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Sample records for activation coordinates multiple

  1. Redox activity and multiple copper(I) coordination of 2His-2Cys oligopeptide.

    PubMed

    Choi, DongWon; Alshahrani, Aisha A; Vytla, Yashodharani; Deeconda, Manogna; Serna, Victor J; Saenz, Robert F; Angel, Laurence A

    2015-02-01

    Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl-His1-Cys2-Tyr3-Pro4-His5-Cys6 was investigated using ion mobility-mass spectrometry (IM-MS) and UV-Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys-Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)](+) which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV-Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides.

  2. Redox activity and multiple copper(I) coordination of 2His-2Cys oligopeptide.

    PubMed

    Choi, DongWon; Alshahrani, Aisha A; Vytla, Yashodharani; Deeconda, Manogna; Serna, Victor J; Saenz, Robert F; Angel, Laurence A

    2015-02-01

    Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl-His1-Cys2-Tyr3-Pro4-His5-Cys6 was investigated using ion mobility-mass spectrometry (IM-MS) and UV-Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys-Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)](+) which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV-Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides. PMID:25800013

  3. Collaborative Construction of Task Activity: Coordinating Multiple Resources in a High School Physics Lab.

    ERIC Educational Resources Information Center

    Ford, Cecilia E.

    1999-01-01

    Documents the collaborative coordination of multiple resources--talk, gesture, and writing--as represented in the interaction among three high school seniors working on a physics laboratory task. Through close analysis of the moment-to-moment construction of task, the study draws attention to complex yet taken-for-granted practices that are…

  4. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  5. Coordination of multiple robot arms

    NASA Technical Reports Server (NTRS)

    Barker, L. K.; Soloway, D.

    1987-01-01

    Kinematic resolved-rate control from one robot arm is extended to the coordinated control of multiple robot arms in the movement of an object. The structure supports the general movement of one axis system (moving reference frame) with respect to another axis system (control reference frame) by one or more robot arms. The grippers of the robot arms do not have to be parallel or at any pre-disposed positions on the object. For multiarm control, the operator chooses the same moving and control reference frames for each of the robot arms. Consequently, each arm then moves as though it were carrying out the commanded motions by itself.

  6. Cadmium Activates Multiple Signaling Pathways That Coordinately Stimulate Akt Activity to Enhance c-Myc mRNA Stability

    PubMed Central

    Tsai, Jia-Shiuan; Chao, Cheng-Han; Lin, Lih-Yuan

    2016-01-01

    Cadmium is a known environmental carcinogen. Exposure of Cd leads to the activation of several proto-oncogenes in cells. We investigated here the mechanism of c-Myc expression in hepatic cells under Cd treatment. The c-Myc protein and mRNA levels increased in dose- and time-dependent manners in HepG2 cells with Cd treatment. This increase was due to an increase in c-Myc mRNA stability. To explore the mechanism involved in enhancing the mRNA stability, several cellular signaling factors that evoked by Cd treatment were analyzed. PI3K, p38, ERK and JNK were activated by Cd. However, ERK did not participate in the Cd-induced c-Myc expression. Further analysis revealed that mTORC2 was a downstream factor of p38. PI3K, JNK and mTORC2 coordinately activated Akt. Akt was phosphorylated at Thr450 in the untreated cells. Cd treatment led to additional phosphorylation at Thr308 and Ser473. Blocking any of the three signaling factors resulted in the reduction of phosphorylation level at all three Akt sites. The activated Akt phosphorylated Foxo1 and allowed the modified protein to translocate into the cytoplasm. We conclude that Cd-induced accumulation of c-Myc requires the activation of several signaling pathways. The signals act coordinately for Akt activation and drive the Foxo1 from the nucleus to the cytoplasm. Reduction of Foxo1 in the nucleus reduces the transcription of its target genes that may affect c-Myc mRNA stability, resulting in a higher accumulation of the c-Myc proteins. PMID:26751215

  7. Programmed cell death in plants: a pathogen-triggered response activated coordinately with multiple defense functions.

    PubMed

    Greenberg, J T; Guo, A; Klessig, D F; Ausubel, F M

    1994-05-20

    In plants, the hypersensitive response (HR) to pathogens involves rapid cell death, which is hypothesized to arise from the activation of a cell death program. We describe mutant A. thaliana plants that contain lesions in a single accelerated cell death (ACD) gene called ACD2 and that bypass the need for pathogen exposure to induce the HR. acd2 plants that develop spontaneous lesions show typical HR characteristics both within the necrotic tissue and within the healthy part of the plant, including: modification of plant cell walls, resistance to bacterial pathogens, and accumulation of defense-related gene transcripts, the signal molecule salicylic acid and an antimicrobial compound. We propose that the ACD2 gene is involved in a pathway(s) that negatively regulates a genetically programmed HR.

  8. Pituitary Adenylate Cyclase-activating Polypeptide (PACAP)/PAC1HOP1 Receptor Activation Coordinates Multiple Neurotrophic Signaling Pathways

    PubMed Central

    May, Victor; Lutz, Eve; MacKenzie, Christopher; Schutz, Kristin C.; Dozark, Kate; Braas, Karen M.

    2010-01-01

    MAPK and Akt pathways are predominant mediators of trophic signaling for many neuronal systems. Among the vasoactive intestinal peptide/secretin/glucagon family of related peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) binding to specific PAC1 receptor isoforms can engage multiple signaling pathways and promote neuroprotection through mechanisms that are not well understood. Using a primary sympathetic neuronal system, the current studies demonstrate that PACAP activation of PAC1HOP1 receptors engages both MAPK and Akt neurotrophic pathways in an integrated program to facilitate neuronal survival after growth factor withdrawal. PACAP not only stimulated prosurvival ERK1/2 and ERK5 activation but also abrogated SAPK/JNK and p38 MAPK signaling in parallel. In contrast to the potent and rapid effects of PACAP in ERK1/2 phosphorylation, PACAP stimulated Akt phosphorylation in a late phase of PAC1HOP1 receptor signaling. From inhibitor and immunoprecipitation analyses, the PACAP/PAC1HOP1 receptor-mediated Akt responses did not represent transactivation mechanisms but appeared to depend on Gαq/phosphatidylinositol 3-kinase γ activity and vesicular internalization pathways. Phosphatidylinositol 3-kinase γ-selective inhibitors blocked PACAP-stimulated Akt phosphorylation in primary neuronal cultures and in PAC1HOP1-overexpressing cell lines; RNA interference-mediated knockdown of the receptor effectors attenuated PACAP-mediated Akt activation. Similarly, perturbation of endocytic pathways also blocked Akt phosphorylation. Between ERK and Akt pathways, PACAP-stimulated Akt signaling was the primary cascade that attenuated cultured neuron apoptosis after growth factor withdrawal. The partitioning of PACAP-mediated Akt signaling in endosomes may be a key mechanism contributing to the high spatial and temporal specificity in signal transduction necessary for survival pathways. PMID:20093365

  9. Shared Activity Coordination

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of real-time, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities in a dynamic environment, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  10. Coordinated Neuronal Activity Enhances Corticocortical Communication.

    PubMed

    Zandvakili, Amin; Kohn, Adam

    2015-08-19

    Relaying neural signals between cortical areas is central to cognition and sensory processing. The temporal coordination of activity in a source population has been suggested to determine corticocortical signaling efficacy, but others have argued that coordination is functionally irrelevant. We reasoned that if coordination significantly influenced signaling, spiking in downstream networks should be preceded by transiently elevated coordination in a source population. We developed a metric to quantify network coordination in brief epochs, and applied it to simultaneous recordings of neuronal populations in cortical areas V1 and V2 of the macaque monkey. Spiking in the input layers of V2 was preceded by brief epochs of elevated V1 coordination, but this was not the case in other layers of V2. Our results indicate that V1 coordination influences its signaling to direct downstream targets, but that coordinated V1 epochs do not propagate through multiple downstream networks as in some corticocortical signaling schemes. PMID:26291164

  11. Continual coordination of shared activities

    NASA Technical Reports Server (NTRS)

    Clement, B. J.; Barrett, A.

    2002-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. For domains with varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently achieve their goals. ShAC (Shared Activity Coordination) is a framework for designing coordination protocols and an algorithm for continually coordinating agents using these protocols during execution. We show how a variety of protocols can be constructed using this framework and describe how ShAC coordinates two rovers and an orbiter in a simulated Mars scenario.

  12. Optimizing plasmonic nanoantennas via coordinated multiple coupling

    PubMed Central

    Lin, Linhan; Zheng, Yuebing

    2015-01-01

    Plasmonic nanoantennas, which can efficiently convert light from free space into sub-wavelength scale with the local field enhancement, are fundamental building blocks for nanophotonic systems. Predominant design methods, which exploit a single type of near- or far-field coupling in pairs or arrays of plasmonic nanostructures, have limited the tunability of spectral response and the local field enhancement. To overcome this limit, we are developing a general strategy towards exploiting the coordinated effects of multiple coupling. Using Au bowtie nanoantenna arrays with metal-insulator-metal configuration as examples, we numerically demonstrate that coordinated design and implementation of various optical coupling effects leads to both the increased tunability in the spectral response and the significantly enhanced electromagnetic field. Furthermore, we design and analyze a refractive index sensor with an ultra-high figure-of-merit (254), a high signal-to-noise ratio and a wide working range of refractive indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption efficiency, high quality factor of up to 114 and a wide range of tunable wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit coordinated multiple coupling will benefit a broad range of applications, including label-free bio-chemical detection, reflective filter, optical trapping, hot-electron generation, and heat-assisted magnetic recording. PMID:26423015

  13. Autonomous Coordination of Science Observations Using Multiple Spacecraft

    NASA Technical Reports Server (NTRS)

    Estlin, Tara A.; Chien, Steve A.; Castano, Rebecca; Gaines, Daniel M.; Doubleday, Joshua R.; Schoolcraft, Joshua B.; Oyake, Amalaye; Vaughs, Ashton G.; Torgerson, Jordan L.; Granville, Charles

    2011-01-01

    This software provides capabilities for autonomous cross-cueing and coordinated observations between multiple orbital and landed assets. Previous work has been done in re-tasking a single Earth orbiter or a Mars rover in response to that craft detecting a science event. This work enables multiple spacecraft to communicate (over a network designed for deep-space communications) and autonomously coordinate the characterization of such a science event. This work investigates a new paradigm of space science campaigns where opportunistic science observations are autonomously coordinated among multiple spacecraft. In this paradigm, opportunistic science detections can be cued by multiple assets where a second asset is requested to take additional observations characterizing the identified surface feature or event. To support this new paradigm, an autonomous science system for multiple spacecraft assets was integrated with the Interplanetary Network DTN (Delay Tolerant Network) to provide communication between spacecraft assets. This technology enables new mission concepts that are not feasible with current technology. The ability to rapidly coordinate activities across spacecraft without requiring ground in the loop enables rapid reaction to dynamic events across platforms, such as a survey instrument followed by a targeted high resolution instrument, as well as regular simultaneous observations.

  14. Continual coordination through shared activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of realtime, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities over the lifetimes of separate missions, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  15. Multiple arm coordination using concurrent processing

    NASA Technical Reports Server (NTRS)

    Basta, Robert A.

    1987-01-01

    The use of concurrent processing for robot arm coordination is considered, and a hierarchically structured set of routines for the completion of coordinated tasks is discussed. Concurrent programming controls interacting concurrent processes by providing techniques to handle the problems of mutual exclusion, synchronization, and communication. The process is demonstrated for the example of the producer-consumer problem. Software supporting a concurrent environment to control a robotic system is being developed in which parallel rather than sequential thought processes are used.

  16. Coordinating Multiple Representations in a Reform Calculus Textbook

    ERIC Educational Resources Information Center

    Chang, Briana L.; Cromley, Jennifer G.; Tran, Nhi

    2015-01-01

    Coordination of multiple representations (CMR) is widely recognized as a critical skill in mathematics and is frequently demanded in reform calculus textbooks. However, little is known about the prevalence of coordination tasks in such textbooks. We coded 707 instances of CMR in a widely used reform calculus textbook and analyzed the distributions…

  17. Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation.

    PubMed

    D'Souza, Anthony D; Parikh, Neal; Kaech, Susan M; Shadel, Gerald S

    2007-12-01

    The quantity and activity of mitochondria vary dramatically in tissues and are modulated in response to changing cellular energy demands and environmental factors. The amount of mitochondrial DNA (mtDNA), which encodes essential subunits of the oxidative phosphorylation complexes required for cellular ATP production, is also tightly regulated, but by largely unknown mechanisms. Using murine T cells as a model system, we have addressed how specific signaling pathways influence mitochondrial biogenesis and mtDNA copy number. T cell receptor (TCR) activation results in a large increase in mitochondrial mass and membrane potential and a corresponding amplification of mtDNA, consistent with a vital role for mitochondrial function for growth and proliferation of these cells. Independent activation of protein kinase C (via PMA) or calcium-related pathways (via ionomycin) had differential and sub-maximal effects on these mitochondrial parameters, as did activation of naïve T cells with proliferative cytokines. Thus, the robust mitochondrial biogenesis response observed upon TCR activation requires synergy of multiple downstream signaling pathways. One such pathway involves AMP-activated protein kinase (AMPK), which we show has an unprecedented role in negatively regulating mitochondrial biogenesis that is mammalian target of rapamycin (mTOR)-dependent. That is, inhibition of AMPK after TCR signaling commences results in excessive, but uncoordinated mitochondrial proliferation. Thus mitochondrial biogenesis is not under control of a single master regulatory circuit, but rather requires the convergence of multiple signaling pathways with distinct downstream consequences on the organelle's structure, composition, and function.

  18. Deductive Coordination of Multiple Geospatial Knowledge Sources

    NASA Astrophysics Data System (ADS)

    Waldinger, R.; Reddy, M.; Culy, C.; Hobbs, J.; Jarvis, P.; Dungan, J. L.

    2002-12-01

    Deductive inference is applied to choreograph the cooperation of multiple knowledge sources to respond to geospatial queries. When no one source can provide an answer, the response may be deduced from pieces of the answer provided by many sources. Examples of sources include (1) The Alexandria Digital Library Gazetteer, a repository that gives the locations for almost six million place names, (2) The Cia World Factbook, an online almanac with basic information about more than 200 countries. (3) The SRI TerraVision 3D Terrain Visualization System, which displays a flight-simulator-like interactive display of geographic data held in a database, (4) The NASA GDACC WebGIS client for searching satellite and other geographic data available through OpenGIS Consortium (OGC) Web Map Servers, and (5) The Northern Arizona University Latitude/Longitude Distance Calculator. Queries are phrased in English and are translated into logical theorems by the Gemini Natural Language Parser. The theorems are proved by SNARK, a first-order-logic theorem prover, in the context of an axiomatic geospatial theory. The theory embodies a representational scheme that takes into account the fact that the same place may have many names, and the same name may refer to many places. SNARK has built-in procedures (RCC8 and the Allen calculus, respectively) for reasoning about spatial and temporal concepts. External knowledge sources may be consulted by SNARK as the proof is in progress, so that most knowledge need not be stored axiomatically. The Open Agent Architecture (OAA) facilitates communication between sources that may be implemented on different machines in different computer languages. An answer to the query, in the form of text or an image, is extracted from the proof. Currently, three-dimensional images are displayed by TerraVision but other displays are possible. The combined system is called Geo-Logica. Some example queries that can be handled by Geo-Logica include: (1) show the

  19. Continual coordination of spacecraft through shared activities

    NASA Technical Reports Server (NTRS)

    Clement, B. J.; Barrett, A. C.

    2002-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus. ShAC (Shared Activity Coordination) is a framework for designing coordination protocols with an algorithm for continually coordinating agents using these protocols during execution. We show how to construct a wide range of protocols using this framework and describe how ShAC coordinates two rovers and an orbiter in a simulated Mars scenario.

  20. Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation

    PubMed Central

    D’Souza, Anthony D.; Parikh, Neal; Kaech, Susan M.; Shadel, Gerald S.

    2009-01-01

    The quantity and activity of mitochondria vary dramatically in tissues and are modulated in response to changing cellular energy demands and environmental factors. The amount of mitochondrial DNA (mtDNA), which encodes essential subunits of the oxidative phosphorylation complexes required for cellular ATP production, is also tightly regulated, but by largely unknown mechanisms. Using murine T cells as a model system, we have addressed how specific signaling pathways influence mitochondrial biogenesis and mtDNA levels. T cell receptor (TCR) activation results in a large increase in mitochondrial mass and membrane potential and a corresponding increase of mtDNA copy number, indicating the vital role for mitochondrial function for the growth and proliferation of these cells. Independent activation of protein kinase C (via PMA) or calcium-related pathways (via ionomycin) had differential and sub-maximal effects on these mitochondrial parameters, as did activation of naïve T cells with proliferative cytokines. Thus, the robust mitochondrial biogenesis response observed upon TCR activation requires synergy of multiple downstream signaling pathways. One such pathway involves AMP-activated protein kinase (AMPK), which we show has an unprecedented role in negatively regulating mitochondrial biogenesis that is mammalian target of rapamycin (mTOR)-dependent. That is, inhibition of AMPK after TCR signaling commences results in excessive, but uncoordinated mitochondrial proliferation. We propose that mitochondrial biogenesis is not under control of a master regulatory circuit, but rather requires the convergence of multiple signaling pathways with distinct downstream consequences on the organelle’s structure, composition, and function. PMID:17890163

  1. Solid-state chemistry of molecular metal oxide clusters. Multiple, sequential C-H activation processes in the hydrogenation of coordinated cyclooctene. Lattice mobility of small organic molecules

    SciTech Connect

    Siedle, A.R.; Newmark, R.A.; Sahyun, M.R.V.; Lyon, P.A.; Hunt, S.L.; Skarjune, R.P. )

    1989-10-25

    Reaction of solid ((Ph{sub 3}P){sub 2}Ir(C{sub 8}H{sub 12})){sub 3}PW{sub 12}O{sub 40} with D{sub 2} gas produces cyclooctane containing up to 16 deuterium atoms. The c-C{sub 8}D{sub n}H{sub 16-n} isotopomer distribution is analyzed by Poisson statistics and interpreted in terms of C-H activation involving Ir-D-C-H exchange in an intermediate species containing coordinated cyclooctene. The results are compared with those from D{sub 2} reduction of ((Ph{sub 3}P){sub 2}Ir(C{sub 8}H{sub 12}))(PF{sub 6}) in the solid state and in acetone solution, in which cases, an additional exchange process operates. Solid-state {sup 2}H NMR shows that, even at low temperatures, small organic molecules such as cyclooctane and benzene undergo nearly isotropic motion.

  2. Lessons Learned from Coordinating Relay Activities at Mars

    NASA Technical Reports Server (NTRS)

    Gladden, Roy E.; Hwang, Pauline; Waggoner, Bruce; McLaughlin, Bruce; Fieseler, Paul; Thomas, Reid; Bigwood, Maria; Herrera, Paul

    2005-01-01

    The Mission Management Office at the Jet Propulsion Laboratory was tasked with coordinating the relay of data between multiple spacecraft at Mars in support of the Mars Exploration Rover Missions in early 2004. The confluence of three orbiters (Mars Global Surveyor, Mars Odyssey, and Mars Express), two rovers (Spirit and Opportunity), and one lander (Beagle 2) has provided a challenging operational scenario that required careful coordination between missions to provide the necessary support and to avoid potential interference during simultaneous relay sessions. As these coordination efforts progressed, several important lessons were learned that should be applied to future Mars relay activities.

  3. Kinematically redundant arm formulations for coordinated multiple arm implementations

    NASA Technical Reports Server (NTRS)

    Bailey, Robert W.; Quiocho, Leslie J.; Cleghorn, Timothy F.

    1990-01-01

    Although control laws for kinematically redundant robotic arms were presented as early as 1969, redundant arms have only recently become recognized as viable solutions to limitations inherent to kinematically sufficient arms. The advantages of run-time control optimization and arm reconfiguration are becoming increasingly attractive as the complexity and criticality of robotic systems continues to progress. A generalized control law for a spatial arm with 7 or more degrees of freedom (DOF) based on Whitney's resolved rate formulation is given. Results from a simulation implementation utilizing this control law are presented. Furthermore, results from a two arm simulation are presented to demonstrate the coordinated control of multiple arms using this formulation.

  4. Coordination and Control of Multiple Spacecraft using Convex Optimization Techniques

    NASA Astrophysics Data System (ADS)

    How, Jonathan P.

    2002-06-01

    Formation flying of multiple spacecraft is an enabling technology for many future space science missions. These future missions will, for example, use the highly coordinated, distributed array of vehicles for earth mapping interferometers and synthetic aperture radar. This thesis presents coordination and control algorithms designed for a fleet of spacecraft. These algorithms are embedded in a hierarchical fleet archi- tecture that includes a high-level coordinator for the fleet maneuvers used to form, re-size, or re-target the formation configuration and low-level controllers to generate and implement the individual control inputs for each vehicle. The trajectory and control problems are posed as linear programming (LP) optimizations to solve for the minimum fuel maneuvers. The combined result of the high-level coordination and low-level controllers is a very flexible optimization framework that can be used off-line to analyze aspects of a mission design and in real-time as part of an on-board autonomous formation flying control system. This thesis also investigates several crit- ical issues associated with the implementation of this formation flying approach. In particular, modifications to the LP algorithms are presented to: include robustness to sensor noise, include actuator constraints, ensure that the optimization solutions are always feasible, and reduce the LP solution times. Furthermore, the dynamics for the control problem are analyzed in terms of two key issues: 1) what dynamics model should be used to specify the desired state to maintain a passive aperture; and 2) what dynamics model should be used in the LP to represent the motion about this state. Several linearized models of the relative dynamics are considered in this analysis, including Hill's equations for circular orbits, modified linear dynamics that partially account for the J2 effects, and Lawden's equations for eccentric orbits.

  5. Optical activity and Alfred Werner's coordination chemistry.

    PubMed

    Ernst, Karl-Heinz; Berke, Heinz

    2011-03-01

    It is widely accepted, that Pasteur's seminal discovery of the opposite optical activity of ammonium sodium tartrate enantiomorphs in solution gave the spark to organic stereochemistry and led to the development of the tetrahedron model by van't Hoff and Le Bel. The proof that chirality is inherently connected to octahedral coordination chemistry fostered greatly Werner's spatial views of metal complexes and his coordination theory. The actual proof of principle was established via separation of diastereomeric camphor sulfonate salts of racemic metal complexes. PMID:20928897

  6. Motion coordination of multiple autonomous vehicles in a spatiotemporal flowfield

    NASA Astrophysics Data System (ADS)

    Peterson, Cameron Kai

    The long-term goal of this research is to provide theoretically justified control strategies to operate autonomous vehicles in spatiotemporal flowfields. The specific objective of this dissertation is to use estimation and nonlinear control techniques to generate decentralized control algorithms that enable motion coordination for multiple autonomous vehicles while operating in a time-varying flowfield. A cooperating team of vehicles can benefit from sharing data and tasking responsibilities. Many existing control algorithms promote collaboration of autonomous vehicles. However, these algorithms often fail to account for the degradation of control performance caused by flowfields. This dissertation presents decentralized multivehicle coordination algorithms designed for operation in a spatially or temporally varying flowfield. Each vehicle is represented using a Newtonian particle traveling in a plane at constant speed relative to the flow and subject to a steering control. Initially, we assume the flowfield is known and describe algorithms that stabilize a circular formation in a time-varying spatially nonuniform flow of moderate intensity. These algorithms are extended by relaxing the assumption that the flow is known: the vehicles dynamically estimate the flow and use that estimate in the control. We propose a distributed estimation and control algorithm comprising a consensus filter to share information gleaned from noisy position measurements, and an information filter to reconstruct a spatially varying flowfield. The theoretical results are illustrated with numerical simulations of circular formation control and validated in outdoor unmanned aerial vehicle (UAV) flight tests.

  7. Update of technical coordinating committee activities

    SciTech Connect

    Alvarado, R.A.

    1995-12-31

    The Technical Coordinating Committee has its origins in the earliest days of implementing the Low-Level Radioactive Waste Policy Act. Between 1982 and 1985, individuals in several of the states felt that coordination among the states would be beneficial to all by affording states a cost-effective method for sharing ideas, discussing alternatives, and presenting solutions to common problems. At the current time, the committee comprises members from each of the sited states. Various compacts, federal agencies, and industry groups participate in committee activities. The Low-Level Management Program provides support for the committee through the provision of logistical support and limited manpower allocation. Activities of the committee have recently focused on waste treatment and minimization technologies. The committee also has worked diligently to see the review of the 3RSTAT computer code completed. The committee has taken a position on various regulatory proposals the past year. The committee expects to continue its work until new sites are brought online.

  8. Coordinating activities between NOAA and other agencies.

    PubMed

    Fritz, A T; Buchman, M F

    1997-11-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and the National Oil and Hazardous Substances Pollution Contingency Plan (NCP) mandate protection of public health, welfare, and the environment at Superfund hazardous waste sites. The NCP requires lead response agenciesto integrate baseline risk assessments into the remedial process that "assess threats to the environment." EPA policy statements direct regional offices to perform thorough, consistent ecological risk assessments, and stress the importance of coordination and technical consultation with the natural resource trustees. As a Federal natural trustee, the National Oceanic and Atmospheric Administration's (NOAA) role and responsibilities within the CERCLA process also are defined and mandated by Federal law. NOAA is responsible for identifying sites in the coastal zone that may affect natural resources, evaluating injury to trust resources, and providing technical advice on assessments and remedial and restoration alternatives. Statutes require lead cleanup agencies and trustee agencies to notify and coordinate with each other during CERCLA response. Over the past ten years, NOAA has gained valuable experience and technical expertise in environmental assessments and in evaluating contaminated aquatic environments. NOAA fulfills its responsibilities through an effective network of Coastal Resource Coordinators (CRCs) who can rapidly respond to local technical requirements and priorities, and coordinate effectively with technical and trustee representatives. In addition to CRCs, an interdisciplinary support group provides technical expertise in the scientific disciplines required to respond to the needs of regional activities. NOAA provides CRCs to coastal EPA regional offices for technical support, and to act as liaisons with Federal and state natural resource trustee agencies. The CRCs help EPA and other lead response agencies identify and assess risks to coastal resources

  9. Coordinating activities between NOAA and other agencies.

    PubMed

    Fritz, A T; Buchman, M F

    1997-11-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and the National Oil and Hazardous Substances Pollution Contingency Plan (NCP) mandate protection of public health, welfare, and the environment at Superfund hazardous waste sites. The NCP requires lead response agenciesto integrate baseline risk assessments into the remedial process that "assess threats to the environment." EPA policy statements direct regional offices to perform thorough, consistent ecological risk assessments, and stress the importance of coordination and technical consultation with the natural resource trustees. As a Federal natural trustee, the National Oceanic and Atmospheric Administration's (NOAA) role and responsibilities within the CERCLA process also are defined and mandated by Federal law. NOAA is responsible for identifying sites in the coastal zone that may affect natural resources, evaluating injury to trust resources, and providing technical advice on assessments and remedial and restoration alternatives. Statutes require lead cleanup agencies and trustee agencies to notify and coordinate with each other during CERCLA response. Over the past ten years, NOAA has gained valuable experience and technical expertise in environmental assessments and in evaluating contaminated aquatic environments. NOAA fulfills its responsibilities through an effective network of Coastal Resource Coordinators (CRCs) who can rapidly respond to local technical requirements and priorities, and coordinate effectively with technical and trustee representatives. In addition to CRCs, an interdisciplinary support group provides technical expertise in the scientific disciplines required to respond to the needs of regional activities. NOAA provides CRCs to coastal EPA regional offices for technical support, and to act as liaisons with Federal and state natural resource trustee agencies. The CRCs help EPA and other lead response agencies identify and assess risks to coastal resources

  10. An efficient algorithm to identify coordinately activated transcription factors.

    PubMed

    Hu, Haiyan

    2010-03-01

    Identification of transcription factor (TF) activities associated with a certain physiological/experimental condition is one of the preliminary steps to reconstruct transcriptional regulatory networks and to identify signal transduction pathways. TF activities are often indicated by the activities of its target genes. Existing studies on identifying TF activities through target genes usually assume the equivalence between co-regulation and co-expression. However, genes with correlated expression profiles may not be co-regulated. In the mean time, although multiple TFs can be activated coordinately, there is a lack of efficient methods to identify coordinately activated TFs. In this paper, we propose an efficient algorithm embedding a dynamic programming procedure to identify a subset of TFs that are potentially coordinately activated under a given condition by utilizing ranked lists of differentially expressed target genes. Applying our algorithm to microarray expression data sets for a number of diseases, our approach found subsets of TFs that are highly likely associated with the given disease processes. PMID:20060041

  11. Coordination of autophagy with other cellular activities

    PubMed Central

    Wang, Yan; Qin, Zheng-hong

    2013-01-01

    The cell biological phenomenon of autophagy has attracted increasing attention in recent years, partly as a consequence of the discovery of key components of its cellular machinery. Autophagy plays a crucial role in a myriad of cellular functions. Autophagy has its own regulatory mechanisms, but this process is not isolated. Autophagy is coordinated with other cellular activities to maintain cell homeostasis. Autophagy is critical for a range of human physiological processes. The multifunctional roles of autophagy are explained by its ability to interact with several key components of various cell pathways. In this review, we focus on the coordination between autophagy and other physiological processes, including the ubiquitin-proteasome system (UPS), energy homeostasis, aging, programmed cell death, the immune responses, microbial invasion and inflammation. The insights gained from investigating autophagic networks should increase our understanding of their roles in human diseases and their potential as targets for therapeutic intervention. PMID:23474706

  12. Coordination of breathing with nonrespiratory activities.

    PubMed

    Bartlett, Donald; Leiter, James C

    2012-04-01

    Many articles in this section of Comprehensive Physiology are concerned with the development and function of a central pattern generator (CPG) for the control of breathing in vertebrate animals. The action of the respiratory CPG is extensively modified by cortical and other descending influences as well as by feedback from peripheral sensory systems. The central nervous system also incorporates other CPGs, which orchestrate a wide variety of discrete and repetitive, voluntary and involuntary movements. The coordination of breathing with these other activities requires interaction and coordination between the respiratory CPG and those governing the nonrespiratory activities. Most of these interactions are complex and poorly understood. They seem to involve both conventional synaptic crosstalk between groups of neurons and fluid identity of neurons as belonging to one CPG or another: neurons that normally participate in breathing may be temporarily borrowed or hijacked by a competing or interrupting activity. This review explores the control of breathing as it is influenced by many activities that are generally considered to be nonrespiratory. The mechanistic detail varies greatly among topics, reflecting the wide variety of pertinent experiments.

  13. Coordinated network activity in the hippocampus.

    PubMed

    Draguhn, Andreas; Keller, Martin; Reichinnek, Susanne

    2014-01-01

    The hippocampus expresses a variety of highly organized network states which bind its individual neurons into collective modes of activity. These patterns go along with characteristic oscillations of extracellular potential known as theta, gamma, and ripple oscillations. Such network oscillations share some important features throughout the entire central nervous system of higher animals: they are restricted to a defined behavioral state, they are mostly generated by subthreshold synaptic activity, and they entrain active neurons to fire action potentials at strictly defined phases of the oscillation cycle, thereby providing a unifying 'zeitgeber' for coordinated multineuronal activity. Recent work from the hippocampus of rodents and humans has revealed how the resulting spatiotemporal patterns support the formation of neuronal assemblies which, in our present understanding, form the neuronal correlate of spatial, declarative, or episodic memories. In this review, we introduce the major types of spatiotemporal activity patterns in the hippocampus, describe the underlying neuronal mechanisms, and illustrate the concept of memory formation within oscillating networks. Research on hippocampus-dependent memory has become a key model system at the interface between cellular and cognitive neurosciences. The next step will be to translate our increasing insight into the mechanisms and systemic functions of neuronal networks into urgently needed new therapeutic strategies. PMID:24777128

  14. Coordinated network activity in the hippocampus.

    PubMed

    Draguhn, Andreas; Keller, Martin; Reichinnek, Susanne

    2014-01-01

    The hippocampus expresses a variety of highly organized network states which bind its individual neurons into collective modes of activity. These patterns go along with characteristic oscillations of extracellular potential known as theta, gamma, and ripple oscillations. Such network oscillations share some important features throughout the entire central nervous system of higher animals: they are restricted to a defined behavioral state, they are mostly generated by subthreshold synaptic activity, and they entrain active neurons to fire action potentials at strictly defined phases of the oscillation cycle, thereby providing a unifying 'zeitgeber' for coordinated multineuronal activity. Recent work from the hippocampus of rodents and humans has revealed how the resulting spatiotemporal patterns support the formation of neuronal assemblies which, in our present understanding, form the neuronal correlate of spatial, declarative, or episodic memories. In this review, we introduce the major types of spatiotemporal activity patterns in the hippocampus, describe the underlying neuronal mechanisms, and illustrate the concept of memory formation within oscillating networks. Research on hippocampus-dependent memory has become a key model system at the interface between cellular and cognitive neurosciences. The next step will be to translate our increasing insight into the mechanisms and systemic functions of neuronal networks into urgently needed new therapeutic strategies.

  15. 30 CFR 229.122 - Coordination of audit activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Coordination of audit activities. 229.122... MANAGEMENT DELEGATION TO STATES Oil and Gas, Onshore Delegation Requirements § 229.122 Coordination of audit... resolution of any coordination problems encountered during the conduct of delegation activities....

  16. Sinusoidal error perturbation reveals multiple coordinate systems for sensorymotor adaptation.

    PubMed

    Hudson, Todd E; Landy, Michael S

    2016-02-01

    A coordinate system is composed of an encoding, defining the dimensions of the space, and an origin. We examine the coordinate encoding used to update motor plans during sensory-motor adaptation to center-out reaches. Adaptation is induced using a novel paradigm in which feedback of reach endpoints is perturbed following a sinewave pattern over trials; the perturbed dimensions of the feedback were the axes of a Cartesian coordinate system in one session and a polar coordinate system in another session. For center-out reaches to randomly chosen target locations, reach errors observed at one target will require different corrections at other targets within Cartesian- and polar-coded systems. The sinewave adaptation technique allowed us to simultaneously adapt both dimensions of each coordinate system (x-y, or reach gain and angle), and identify the contributions of each perturbed dimension by adapting each at a distinct temporal frequency. The efficiency of this technique further allowed us to employ perturbations that were a fraction the size normally used, which avoids confounding automatic adaptive processes with deliberate adjustments made in response to obvious experimental manipulations. Subjects independently corrected errors in each coordinate in both sessions, suggesting that the nervous system encodes both a Cartesian- and polar-coordinate-based internal representation for motor adaptation. The gains and phase lags of the adaptive responses are not readily explained by current theories of sensory-motor adaptation.

  17. Modeling Coordination in Multiple Simultaneous Latent Change Scores

    PubMed Central

    Butner, Jonathan E.; Berg, Cynthia A.; Baucom, Brian R.; Wiebe, Deborah J.

    2016-01-01

    Coordination is a taxonomy of how processes change together through time. It depicts the changes of two or more variables in terms of the strength and consistency of their covariation, the directionality of their covariation (i.e., do increases in one variable correspond with increases [in-phase] or decreases [anti-phase] in the other variable), and the timing of their covariation (i.e., do both variables change at the same rate or does one variable change faster than the other). Current methods are able to characterize some, but not all, of these aspects of coordination and provide incomplete information as a result. The current study addresses this limitation by demonstrating that multivariate latent change score models can be used to fully differentiate all possible coordination patterns. Furthermore, one can then expand coordination beyond the two outcome case to test arrangements of underlying coordination mechanisms or patterns. Examples using two simultaneous latent change score models and four simultaneous latent change score models illustrate this approach within the context of adolescents and parents regulating type 1 diabetes. PMID:26735358

  18. 34 CFR 75.580 - Coordination with other activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Coordination with other activities. 75.580 Section 75.580 Education Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS What Conditions Must Be Met by a Grantee? Indirect Cost Rates § 75.580 Coordination with other activities. A...

  19. Framework for coordination of activities in dynamic situations

    NASA Astrophysics Data System (ADS)

    Franke, Jörn; Charoy, François; El Khoury, Paul

    2013-02-01

    Recent disasters, such as Hurricane Katrina in 2005, have shown several issues for the coordination of human activities in these dynamic situations. Contemporary tools for the coordination used in the disaster response, such as e-mail, Whiteboards or phones, only allow for unstructured coordination, which can cause coordination problems. Hence, we discuss about the current information systems for coordinating the activities in a structured manner and identify their weaknesses in the context of a process modelling effort conducted together with experienced disaster managers. Afterwards, we propose a framework for coordination of activities in dynamic situations. The framework presented in this paper has been implemented as an extension to an open collaboration service. This shows how it can be used in the context of other tools required for disaster response management, such as maps, pictures or videos of the situation. The work described here is the foundation for enabling inter-organisational coordination of activities relevant in other domains, e.g. enterprise support processes, production processes or distributed software development projects. Furthermore, comments by disaster managers show that the concepts are relevant for their work. The expected impact is a more effective and efficient coordination of human activities in dynamic situations by structuring what needs to be coordinated.

  20. 20 CFR 631.37 - Coordination activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Services under this part shall be integrated or coordinated with services and payments made available under...) and the unemployment compensation system consistent with the limitation on administrative expenses... compensation system and worker readjustment programs (section 314(f)). (c) Services under this part shall...

  1. Multiplayer Activities That Develop Mathematical Coordination.

    ERIC Educational Resources Information Center

    Bricker, Lauren J.; Tanimoto, Steven L.; Rothenberg, Alex I.; Hutama, Danny C.; Wong, Tina H.

    Four computer applications are presented that encourage students to develop "mathematical coordination"--the ability to manipulate numerical variables in cooperation with other students so as to achieve a definite goal. The programs enable a form of computer-supported cooperative learning (CSCL). This paper describes the rationale and design of…

  2. Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

    PubMed Central

    Murray, Heath; Koh, Alan

    2014-01-01

    In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes. PMID:25340815

  3. 34 CFR 76.580 - Coordination with other activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Coordination with other activities. 76.580 Section 76.580 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must Be Met by the State and Its Subgrantees? Indirect Cost Rates § 76.580 Coordination with...

  4. Meta-Coordination Activities: Exploring Articulation Work in Hospitals

    ERIC Educational Resources Information Center

    Abraham, Joanna

    2010-01-01

    Coordination of distributed activities is central to organizational work. The effective functioning of organizations hinges on their ability to manage interdependencies both within (intra-) and between (inter-) various departments. However, more than just the management of these individual dependencies is required for smooth coordination in…

  5. Genetic algorithm for multiple bus line coordination on urban arterial.

    PubMed

    Yang, Zhen; Wang, Wei; Chen, Shuyan; Ding, Haoyang; Li, Xiaowei

    2015-01-01

    Bus travel time on road section is defined and analyzed with the effect of multiple bus lines. An analytical model is formulated to calculate the total red time a bus encounters when travelling along the arterial. Genetic algorithm is used to optimize the offset scheme of traffic signals to minimize the total red time that all bus lines encounter in two directions of the arterial. The model and algorithm are applied to the major part of Zhongshan North Street in the city of Nanjing. The results show that the methods in this paper can reduce total red time of all the bus lines by 31.9% on the object arterial and thus improve the traffic efficiency of the whole arterial and promote public transport priority.

  6. Genetic algorithm for multiple bus line coordination on urban arterial.

    PubMed

    Yang, Zhen; Wang, Wei; Chen, Shuyan; Ding, Haoyang; Li, Xiaowei

    2015-01-01

    Bus travel time on road section is defined and analyzed with the effect of multiple bus lines. An analytical model is formulated to calculate the total red time a bus encounters when travelling along the arterial. Genetic algorithm is used to optimize the offset scheme of traffic signals to minimize the total red time that all bus lines encounter in two directions of the arterial. The model and algorithm are applied to the major part of Zhongshan North Street in the city of Nanjing. The results show that the methods in this paper can reduce total red time of all the bus lines by 31.9% on the object arterial and thus improve the traffic efficiency of the whole arterial and promote public transport priority. PMID:25663837

  7. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.

    PubMed

    McElvain, Lauren E; Faulstich, Michael; Jeanne, James M; Moore, Jeffrey D; du Lac, Sascha

    2015-03-01

    Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.

  8. Method for the evaluation of structure-activity relationship information associated with coordinated activity cliffs.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2014-08-14

    Activity cliffs are generally defined as pairs of active compounds having a large difference in potency. Although this definition of activity cliffs focuses on compound pairs, the vast majority of cliffs are formed in a coordinated manner. This means that multiple highly and weakly potent compounds form series of activity cliffs, which often overlap. In activity cliff networks, coordinated cliffs emerge as disjoint activity cliff clusters. Recently, we have identified all cliff clusters from current bioactive compounds and analyzed their topologies. For structure-activity relationship (SAR) analysis, activity cliff clusters are of high interest, since they contain more SAR information than cliffs that are individually considered. For medicinal chemistry applications, a key question becomes how to best extract SAR information from activity cliff clusters. This represents a challenging problem, given the complexity of many activity cliff configurations. Herein we introduce a generally applicable methodology to organize activity cliff clusters on the basis of structural relationships, prioritize clusters, and systematically extract SAR information from them. PMID:25014781

  9. Family-centered care coordination for children with special needs across multiple settings.

    PubMed

    Lindeke, Linda L; Leonard, Barbara J; Presler, Betty; Garwick, Ann

    2002-01-01

    Care coordination is a process that involves assessment, planning, implementation, evaluation, education, monitoring, support, and advocacy. Pediatric nurse practitioners (PNPs) are well positioned to coordinate care but may not be well educated about potential conflicts of interest in balancing cost-containment constraints with obtaining maximum quality and quantity of care for children and families with complex needs. The philosophy of family-centered care is embodied in some care coordination models and absent in others. PNPs who aim to support families of children with special health care needs need to understand the complexity of interacting with multiple care coordination models across health and educational settings. PNPs may act as change agents to infuse family-centered care principles into existing and future care coordination models. PMID:12436098

  10. Activities and Participation in Children with Developmental Coordination Disorder: A Systematic Review

    ERIC Educational Resources Information Center

    Magalhaes, L. C.; Cardoso, A. A.; Missiuna, C.

    2011-01-01

    Purpose: To systematically review all literature published in peer reviewed journals from January 1995 to July 2008 in order to summarize and describe the activity limitations and participation restrictions of children with developmental coordination disorder (DCD). Methods: Multiple databases were systematically searched for articles related to…

  11. Antibacterial activity of silver camphorimine coordination polymers.

    PubMed

    Cardoso, João M S; Galvão, Adelino M; Guerreiro, Soraia I; Leitão, Jorge H; Suarez, Ana C; Carvalho, M Fernanda N N

    2016-04-28

    Five new silver camphorimine complexes of general formula [Ag(NO3)(Y)L] were synthesized and fully characterized using spectroscopic and analytical techniques. The structure of [Ag(NO3)(OC10H14NC6H4NC10H14O)] () was analyzed using single crystal X-ray diffraction, showing that it arranges as a coordination polymer formed by sequential Ag(NO3) units bridged by the bi-camphor ligand (). The antimicrobial properties of the new complexes were screened using the disk diffusion method and their Minimal Inhibitory Concentrations (MIC) were assessed against selected bacterial strains of the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli, Pseudomonas aeruginosa, and Burkholderia contaminans. The lowest MICs were observed for , with estimated values of 72, 20, 32 and 19 μg mL(-1) for S. aureus, E. coli, B. contaminans, and P. aeruginosa, respectively. In the case of S. aureus, similar MIC values were obtained for silver nitrate and compound . All five compounds were bactericidal when used in concentrations equal or above the MIC value, as found by enumerating the total colony forming units (CFUs) after incubation in their presence. PMID:27007331

  12. Coordination and standardization of federal sedimentation activities

    USGS Publications Warehouse

    Glysson, G. Douglas; Gray, John R.

    1997-01-01

    - precipitation information critical to water resources management. Memorandum M-92-01 covers primarily freshwater bodies and includes activities, such as "development and distribution of consensus standards, field-data collection and laboratory analytical methods, data processing and interpretation, data-base management, quality control and quality assurance, and water- resources appraisals, assessments, and investigations." Research activities are not included.

  13. CRASP: a program for analysis of coordinated substitutions in multiple alignments of protein sequences.

    PubMed

    Afonnikov, Dmitry A; Kolchanov, Nikolay A

    2004-07-01

    Recent results suggest that during evolution certain substitutions at protein sites may occur in a coordinated manner due to interactions between amino acid residues. Information on these coordinated substitutions may be useful for analysis of protein structure and function. CRASP is an Internet-available software tool for the detection and analysis of coordinated substitutions in multiple alignments of protein sequences. The approach is based on estimation of the correlation coefficient between the values of a physicochemical parameter at a pair of positions of sequence alignment. The program enables the user to detect and analyze pairwise relationships between amino acid substitutions at protein sequence positions, estimate the contribution of the coordinated substitutions to the evolutionary invariance or variability in integral protein physicochemical characteristics such as the net charge of protein residues and hydrophobic core volume. The CRASP program is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/crasp/.

  14. Fractions as the Coordination of Multiplicatively Related Quantities: A Cross-Sectional Study of Children's Thinking

    ERIC Educational Resources Information Center

    Empson, Susan B.; Junk, Debra; Dominguez, Higinio; Turner, Erin

    2006-01-01

    Although equal sharing problems appear to support the development of fractions as multiplicative structures, very little work has examined how children's informal solutions reflect this possibility. The primary goal of this study was to analyze children's coordination of two quantities (number of people sharing and number of things being shared)…

  15. Coordinating Computing, Network and Archiving activities within INAF

    NASA Astrophysics Data System (ADS)

    Pasian, F.; Bodo, G.; Fini, L.; Garilli, B.; Longo, G.; Massimino, P.; Nanni, M.; Smareglia, R.

    When INAF was reformed, it was decided to create a `Computing, Network and Archives Service' within the Projects Department, in order to coordinate all computer-related activities and to properly harmonize management and development policies in the field. A `Computing, Network and Archives Committee' was immediately nominated for the duration of one year to cope with the immediate needs. The Committee has the task of identifying and making operational strategies to coordinate activities in the areas of interest, improving service to all users, implementing synergies and economies, while guaranteeing a single INAF contact point for all external institutions working in the field.

  16. Euro-VO-Coordination of virtual observatory activities in Europe

    NASA Astrophysics Data System (ADS)

    Genova, Françoise; Allen, Mark G.; Arviset, Christophe; Lawrence, Andy; Pasian, Fabio; Solano, Enrique; Wambsganss, Joachim

    2015-06-01

    The European Virtual Observatory Euro-VO has been coordinating European VO activities through a series of projects co-funded by the European Commission over the last 15 years. The bulk of VO work in Europe is ensured by the national VO initiatives and those of intergovernmental agencies. VO activities at the European level coordinate the work in support of the three "pillars" of the Virtual Observatory: support to the scientific community, take-up by the data providers, and technological activities. Several Euro-VO projects have also provided direct support to selected developments and prototyping. This paper explains the methodology used by Euro-VO over the years. It summarises the activities which were performed and their evolutions at different stages of the development of the VO, explains the Euro-VO role with respect to the international and national levels of VO activities, details the lessons learnt for best practices for the coordination of the VO building blocks, and the liaison with other European initiatives, documenting the added-value of European coordination. Finally, the current status and next steps of Euro-VO are briefly addressed.

  17. Setting standards at the forefront of delivery system reform: aligning care coordination quality measures for multiple chronic conditions.

    PubMed

    DuGoff, Eva H; Dy, Sydney; Giovannetti, Erin R; Leff, Bruce; Boyd, Cynthia M

    2013-01-01

    The primary study objective is to assess how three major health reform care coordination initiatives (Accountable Care Organizations, Independence at Home, and Community-Based Care Transitions) measure concepts critical to care coordination for people with multiple chronic conditions. We find that there are major differences in quality measurement across these three large and politically important programs. Quality measures currently used or proposed for these new health reform-related programs addressing care coordination primarily capture continuity of care. Other key areas of care coordination, such as care transitions, patient-centeredness, and cross-cutting care across multiple conditions are infrequently addressed. The lack of a comprehensive and consistent measure set for care coordination will pose challenges for healthcare providers and policy makers who seek, respectively, to provide and reward well-coordinated care. In addition, this heterogeneity in measuring care coordination quality will generate new information, but will inhibit comparisons between these care coordination programs.

  18. A three-echelon supply chain coordination with quantity discounts for multiple items

    NASA Astrophysics Data System (ADS)

    Chang, Ching-Ter; Chiou, Chei-Chang; Yang, Ya-Wen; Chang, Shu-Chin; Wang, Wanncherng

    2010-05-01

    This study derives an integrated model for three-echelon supply chain (i.e. single-supplier, single-vendor and multi-retailer) to minimise the joint costs of all participants associated with holding costs, ordering costs, and purchasing costs. We particularly emphasise that quantity discounts and joint replenishment policies can be utilised as coordination mechanisms among all parties. In addition, a linearisation approach and mixed integer method are developed not only to obtain an executable integer solution for a finite planning horizon problem but also to simplify the conventional multiple-step procedure used in the quantity discount. The result indicates that the coordination and consolidation of orders can lead to the total cost reduction. Finally, a numerical example is given to illustrate the benefits of orders coordination and consolidation.

  19. A new redox-active coordination polymer with cobalticinium dicarboxylate.

    PubMed

    Kondo, Mitsuru; Hayakawa, Yuri; Miyazawa, Makoto; Oyama, Aiko; Unoura, Kei; Kawaguchi, Hiroyuki; Naito, Tetsuyoshi; Maeda, Kenji; Uchida, Fumio

    2004-09-20

    A new two-dimensional coordination polymer with cobalticinium 1,1'-dicarboxylate (ccdc) incorporated in the framework has been prepared, the ccdc functioning as unique monoanionic dicarboxylate ligands. The compound shows a high redox activity based on the ccdc units.

  20. 23 CFR 450.208 - Coordination of planning process activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... CFR part 500. (e) States may apply asset management principles and techniques in establishing planning... 23 Highways 1 2010-04-01 2010-04-01 false Coordination of planning process activities. 450.208 Section 450.208 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PLANNING...

  1. Multiple target three-dimensional coordinate estimation for bistatic MIMO radar with uniform linear receive array

    NASA Astrophysics Data System (ADS)

    Li, Jun; Li, Huan; Long, Libing; Liao, Guisheng; Griffiths, Hugh

    2013-12-01

    A novel scheme to achieve three-dimensional (3D) target location in bistatic radar systems is evaluated. The proposed scheme develops the additional information of the bistatic radar, that is the transmit angles, to estimate the 3D coordinates of the targets by using multiple-input multiple-output techniques with a uniform circular array on transmit and a uniform linear array on receive. The transmit azimuth, transmit elevation angles and receive cone angle of the targets are first extracted from the receive data and the 3D coordinates are then calculated on the basis of these angles. The geometric dilution of precision which is based on the root Cramer-Rao bound of the angles, is derived to evaluate the performance bound of the proposed scheme. Further, an ESPRIT based algorithm is developed to estimate the 3D coordinates of the targets. The advantages of this scheme are that the hardware of the receive array is reduced and the 3D coordinates of the targets can be estimated in the absence of the range information in bistatic radar. Simulations and analysis show that the proposed scheme has potential to achieve good performance with low-frequency radar.

  2. Coordinating the Bidding Strategy in Multiissue Multiobject Negotiation With Single and Multiple Providers.

    PubMed

    Mansour, Khalid; Kowalczyk, Ryszard

    2015-10-01

    This paper addresses the problem of flexible procurement of multiple distinct services characterized by multiple nonfunctional characteristics, i.e., quality-of-service attributes. We consider the one-to-many negotiation approach as a flexible method for procuring multiple different services by a buyer agent. We address the problem of coordinating the bidding strategy amongst multiple concurrent negotiations and propose novel dynamic negotiation strategies. The proposed strategies consider the behaviors of the opponents of the current negotiation encounter in managing the local reservation values of the common negotiation issues (attributes) of different services. Most previous works consider the problem of negotiation over a single object characterized by one or more issues. We extend our previous work and investigate a more complex situation where a buyer agent negotiates over multiple distinct services given that each service has multiple negotiation issues and multiple possible providers. The experimental results show evidence for the effectiveness and robustness of our dynamic negotiation strategies under various negotiation environments.

  3. Introducing Multiplication and Division, Kangaroos and Numbers: MINNEMAST Coordinated Mathematics - Science Series, Unit 17.

    ERIC Educational Resources Information Center

    Ihrig, Elizabeth A., Ed.

    This volume is the seventeenth in a series of 29 coordinated MINNEMAST units in mathematics and science for kindergarten and the primary grades. Intended for use by second-grade teachers, this unit guide provides a summary and overview of the unit, a list of materials needed, and descriptions of five groups of activities. The purposes and…

  4. Attraction and social coordination: mutual entrainment of vocal activity rhythms.

    PubMed

    McGarva, Andrew R; Warner, Rebecca M

    2003-05-01

    To investigate factors that affect the mutual entrainment of vocal activity rhythms, female general psychology students paired according to attitude similarity questionnaires engaged in 40-minute introductory conversations. Fourier analyses performed on speakers' on-off vocal activity demonstrated periodic oscillations in talkativeness. Although some dyads coordinated their vocal activity rhythms, speech accommodation was not predicted by attitude similarity or attraction and did not affect ratings of conversation quality. These rhythms of dialogue appear resistant to change, their behavioral momentum rooted perhaps in an underlying chronobiology. PMID:12845943

  5. Attraction and social coordination: mutual entrainment of vocal activity rhythms.

    PubMed

    McGarva, Andrew R; Warner, Rebecca M

    2003-05-01

    To investigate factors that affect the mutual entrainment of vocal activity rhythms, female general psychology students paired according to attitude similarity questionnaires engaged in 40-minute introductory conversations. Fourier analyses performed on speakers' on-off vocal activity demonstrated periodic oscillations in talkativeness. Although some dyads coordinated their vocal activity rhythms, speech accommodation was not predicted by attitude similarity or attraction and did not affect ratings of conversation quality. These rhythms of dialogue appear resistant to change, their behavioral momentum rooted perhaps in an underlying chronobiology.

  6. From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

    PubMed Central

    Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya

    2014-01-01

    In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775

  7. Relationships between coordination, active drag and propelling efficiency in crawl.

    PubMed

    Seifert, Ludovic; Schnitzler, Christophe; Bideault, Gautier; Alberty, Morgan; Chollet, Didier; Toussaint, Huub Martin

    2015-02-01

    This study examines the relationships between the index of coordination (IdC) and active drag (D) assuming that at constant average speed, average drag equals average propulsion. The relationship between IdC and propulsive efficiency (ep) was also investigated at maximal speed. Twenty national swimmers completed two incremental speed tests swimming front crawl with arms only in free condition and using a measurement of active drag system. Each test was composed of eight 25-m bouts from 60% to 100% of maximal intensity whereby each lap was swum at constant speed. Different regression models were tested to analyse IdC-D relationship. Correlation between IdC and ep was calculated. IdC was linked to D by linear regression (IdC=0.246·D-27.06; R(2)=0.88, P<.05); swimmers switched from catch-up to superposition coordination mode at a speed of ∼1.55ms(-1) where average D is ∼110N. No correlation between IdC and ep at maximal speed was found. The intra-individual analysis revealed that coordination plays an important role in scaling propulsive forces with higher speed levels such that these are adapted to aquatic resistance. Inter-individual analysis showed that high IdC did not relate to a high ep suggesting an individual optimization of force and power generation is at play to reach high speeds.

  8. Coordinating complex decision support activities across distributed applications

    NASA Technical Reports Server (NTRS)

    Adler, Richard M.

    1994-01-01

    Knowledge-based technologies have been applied successfully to automate planning and scheduling in many problem domains. Automation of decision support can be increased further by integrating task-specific applications with supporting database systems, and by coordinating interactions between such tools to facilitate collaborative activities. Unfortunately, the technical obstacles that must be overcome to achieve this vision of transparent, cooperative problem-solving are daunting. Intelligent decision support tools are typically developed for standalone use, rely on incompatible, task-specific representational models and application programming interfaces (API's), and run on heterogeneous computing platforms. Getting such applications to interact freely calls for platform independent capabilities for distributed communication, as well as tools for mapping information across disparate representations. Symbiotics is developing a layered set of software tools (called NetWorks! for integrating and coordinating heterogeneous distributed applications. he top layer of tools consists of an extensible set of generic, programmable coordination services. Developers access these services via high-level API's to implement the desired interactions between distributed applications.

  9. Pinatubo Emulation in Multiple Models (POEMs): co-ordinated experiments in the ISA-MIP model intercomparison activity component of the SPARC Stratospheric Sulphur and it's Role in Climate initiative (SSiRC)

    NASA Astrophysics Data System (ADS)

    Lee, Lindsay; Mann, Graham; Carslaw, Ken; Toohey, Matthew; Aquila, Valentina

    2016-04-01

    The World Climate Research Program's SPARC initiative has a new international activity "Stratospheric Sulphur and its Role in Climate" (SSiRC) to better understand changes in stratospheric aerosol and precursor gaseous sulphur species. One component of SSiRC involves an intercomparison "ISA-MIP" of composition-climate models that simulate the stratospheric aerosol layer interactively. Within PoEMS each modelling group will run a "perturbed physics ensemble" (PPE) of interactive stratospheric aerosol (ISA) simulations of the Pinatubo eruption, varying several uncertain parameters associated with the eruption's SO2 emissions and model processes. A powerful new technique to quantify and attribute sources of uncertainty in complex global models is described by Lee et al. (2011, ACP). The analysis uses Gaussian emulation to derive a probability density function (pdf) of predicted quantities, essentially interpolating the PPE results in multi-dimensional parameter space. Once trained on the ensemble, a Monte Carlo simulation with the fast Gaussian emulator enabling a full variance-based sensitivity analysis. The approach has already been used effectively by Carslaw et al., (2013, Nature) to quantify the uncertainty in the cloud albedo effect forcing from a 3D global aerosol-microphysics model allowing to compare the sensitivy of different predicted quantities to uncertainties in natural and anthropogenic emissions types, and structural parameters in the models. Within ISA-MIP, each group will carry out a PPE of runs, with the subsequent analysis with the emulator assessing the uncertainty in the volcanic forcings predicted by each model. In this poster presentation we will give an outline of the "PoEMS" analysis, describing the uncertain parameters to be varied and the relevance to further understanding differences identified in previous international stratospheric aerosol assessments.

  10. Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma

    PubMed Central

    Aldiri, Issam; Ajioka, Itsuki; Xu, Beisi; Zhang, Jiakun; Chen, Xiang; Benavente, Claudia; Finkelstein, David; Johnson, Dianna; Akiyama, Jennifer; Pennacchio, Len A.; Dyer, Michael A.

    2015-01-01

    Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms. PMID:26628093

  11. Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma

    SciTech Connect

    Aldiri, Issam; Ajioka, Itsuki; Xu, Beisi; Zhang, Jiakun; Chen, Xiang; Benavente, Claudia; Finkelstein, David; Johnson, Dianna; Akiyama, Jennifer; Pennacchio, Len A.; Dyer, Michael A.

    2015-12-01

    Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulate retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. In conclusion, ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.

  12. Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa.

    PubMed

    Chen, Yicai; Yuan, Mingjun; Mohanty, Anee; Yam, Joey Kuok Hoong; Liu, Yang; Chua, Song Lin; Nielsen, Thomas E; Tolker-Nielsen, Tim; Givskov, Michael; Cao, Bin; Yang, Liang

    2015-06-01

    The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One intrinsic feature of c-di-GMP signalling is the abundance of DGCs and PDEs encoded by many bacterial species. It is unclear whether the different DGCs or PDEs coordinately establish the c-di-GMP regulation or function independently of each other. Here, we provide evidence that multiple DGCs are involved in regulation of c-di-GMP on synthesis of the major iron siderophore pyoverdine in Pseudomonas aeruginosa. Constitutive expression of the WspG or YedQ DGC in P. aeruginosa is able to induce its pyoverdine synthesis. Induction of pyoverdine synthesis by high intracellular c-di-GMP depends on the synthesis of exopolysaccharides and another two DGCs, SiaD and SadC. SiaD was found to boost the c-di-GMP synthesis together with constitutively expressing YedQ. The exopolysaccharides and the SiaD DGC were found to modulate the expression of the RsmY/RsmZ ncRNAs. Induction of the RsmY/RsmZ ncRNAs might enhance the pyoverdine synthesis through SadC. Our study sheds light on a novel multiple DGC-coordinated c-di-GMP regulatory mechanism of bacteria. PMID:25683454

  13. Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma

    DOE PAGES

    Aldiri, Issam; Ajioka, Itsuki; Xu, Beisi; Zhang, Jiakun; Chen, Xiang; Benavente, Claudia; Finkelstein, David; Johnson, Dianna; Akiyama, Jennifer; Pennacchio, Len A.; et al

    2015-12-01

    Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulatemore » retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. In conclusion, ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.« less

  14. Classification of physical activities based on body-segments coordination.

    PubMed

    Fradet, Laetitia; Marin, Frederic

    2016-09-01

    Numerous innovations based on connected objects and physical activity (PA) monitoring have been proposed. However, recognition of PAs requires robust algorithm and methodology. The current study presents an innovative approach for PA recognition. It is based on the heuristic definition of postures and the use of body-segments coordination obtained through external sensors. The first part of this study presents the methodology required to define the set of accelerations which is the most appropriate to represent the particular body-segments coordination involved in the chosen PAs (here walking, running, and cycling). For that purpose, subjects of different ages and heterogeneous physical conditions walked, ran, cycled, and performed daily activities at different paces. From the 3D motion capture, vertical and horizontal accelerations of 8 anatomical landmarks representative of the body were computed. Then, the 680 combinations from up to 3 accelerations were compared to identify the most appropriate set of acceleration to discriminate the PAs in terms of body segment coordinations. The discrimination was based on the maximal Hausdorff Distance obtained between the different set of accelerations. The vertical accelerations of both knees demonstrated the best PAs discrimination. The second step was the proof of concept, implementing the proposed algorithm to classify PAs of new group of subjects. The originality of the proposed algorithm is the possibility to use the subject's specific measures as reference data. With the proposed algorithm, 94% of the trials were correctly classified. In conclusion, our study proposed a flexible and extendable methodology. At the current stage, the algorithm has been shown to be valid for heterogeneous subjects, which suggests that it could be deployed in clinical or health-related applications regardless of the subjects' physical abilities or characteristics.

  15. Classification of physical activities based on body-segments coordination.

    PubMed

    Fradet, Laetitia; Marin, Frederic

    2016-09-01

    Numerous innovations based on connected objects and physical activity (PA) monitoring have been proposed. However, recognition of PAs requires robust algorithm and methodology. The current study presents an innovative approach for PA recognition. It is based on the heuristic definition of postures and the use of body-segments coordination obtained through external sensors. The first part of this study presents the methodology required to define the set of accelerations which is the most appropriate to represent the particular body-segments coordination involved in the chosen PAs (here walking, running, and cycling). For that purpose, subjects of different ages and heterogeneous physical conditions walked, ran, cycled, and performed daily activities at different paces. From the 3D motion capture, vertical and horizontal accelerations of 8 anatomical landmarks representative of the body were computed. Then, the 680 combinations from up to 3 accelerations were compared to identify the most appropriate set of acceleration to discriminate the PAs in terms of body segment coordinations. The discrimination was based on the maximal Hausdorff Distance obtained between the different set of accelerations. The vertical accelerations of both knees demonstrated the best PAs discrimination. The second step was the proof of concept, implementing the proposed algorithm to classify PAs of new group of subjects. The originality of the proposed algorithm is the possibility to use the subject's specific measures as reference data. With the proposed algorithm, 94% of the trials were correctly classified. In conclusion, our study proposed a flexible and extendable methodology. At the current stage, the algorithm has been shown to be valid for heterogeneous subjects, which suggests that it could be deployed in clinical or health-related applications regardless of the subjects' physical abilities or characteristics. PMID:27441831

  16. The Telesupervised Adaptive Ocean Sensor Fleet (TAOSF) Architecture: Coordination of Multiple Oceanic Robot Boats

    NASA Technical Reports Server (NTRS)

    Elfes, Alberto; Podnar, Gregg W.; Dolan, John M.; Stancliff, Stephen; Lin, Ellie; Hosler, Jeffrey C.; Ames, Troy J.; Higinbotham, John; Moisan, John R.; Moisan, Tiffany A.; Kulczycki, Eric A.

    2008-01-01

    Earth science research must bridge the gap between the atmosphere and the ocean to foster understanding of Earth s climate and ecology. Ocean sensing is typically done with satellites, buoys, and crewed research ships. The limitations of these systems include the fact that satellites are often blocked by cloud cover, and buoys and ships have spatial coverage limitations. This paper describes a multi-robot science exploration software architecture and system called the Telesupervised Adaptive Ocean Sensor Fleet (TAOSF). TAOSF supervises and coordinates a group of robotic boats, the OASIS platforms, to enable in-situ study of phenomena in the ocean/atmosphere interface, as well as on the ocean surface and sub-surface. The OASIS platforms are extended deployment autonomous ocean surface vehicles, whose development is funded separately by the National Oceanic and Atmospheric Administration (NOAA). TAOSF allows a human operator to effectively supervise and coordinate multiple robotic assets using a sliding autonomy control architecture, where the operating mode of the vessels ranges from autonomous control to teleoperated human control. TAOSF increases data-gathering effectiveness and science return while reducing demands on scientists for robotic asset tasking, control, and monitoring. The first field application chosen for TAOSF is the characterization of Harmful Algal Blooms (HABs). We discuss the overall TAOSF architecture, describe field tests conducted under controlled conditions using rhodamine dye as a HAB simulant, present initial results from these tests, and outline the next steps in the development of TAOSF.

  17. A Lamellar Coordination Polymer with Remarkable Catalytic Activity.

    PubMed

    Mendes, Ricardo F; Antunes, Margarida M; Silva, Patrícia; Barbosa, Paula; Figueiredo, Filipe; Linden, Anthony; Rocha, João; Valente, Anabela A; Almeida Paz, Filipe A

    2016-09-01

    A positively charged lamellar coordination polymer based on a flexible triphosphonic acid linker is reported. [Gd(H4 nmp)(H2 O)2 ]Cl⋅2 H2 O (1) [H6 nmp=nitrilotris(methylenephosphonic acid)] was obtained by a one-pot approach by using water as a green solvent and by forcing the inclusion of additional acid sites by employing HCl in the synthesis. Compound 1 acts as a versatile heterogeneous acid catalyst with outstanding activity in organic reactions such as alcoholysis of styrene oxide, acetalization of benzaldehyde and cyclohexanaldehyde and ketalization of cyclohexanone. For all reaction systems, very high conversions were reached (92-97 %) in only 15-30 min under mild conditions (35 °C, atmospheric pressure). The coordination polymer exhibits a protonic conductivity of 1.23×10(-5)  S cm(-1) at 98 % relative humidity and 40 °C. PMID:27505712

  18. 48 CFR 2452.237-72 - Coordination of data collection activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Coordination of data... Provisions and Clauses 2452.237-72 Coordination of data collection activities. As prescribed in 2437.110(c... identical information from ten or more public respondents. Coordination of Data Collection Activities...

  19. 75 FR 15496 - Agency Information Collection (Care Coordination Home Telehealth (CCHT)) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Care Coordination Home Telehealth (CCHT)) Activity Under OMB Review...).'' SUPPLEMENTARY INFORMATION: Title: Care Coordination Home Telehealth (CCHT) Patient Satisfaction Survey, VA...

  20. 75 FR 2595 - Proposed Information Collection (Care Coordination Home Telehealth (CCHT) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Care Coordination Home Telehealth (CCHT) Activity: Comment... use of other forms of information technology. Title: Care Coordination Home Telehealth (CCHT)...

  1. Recommendations for physical activity in patients with multiple sclerosis.

    PubMed

    Petajan, J H; White, A T

    1999-03-01

    For many years, patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system, have been advised to avoid exercise. MS is believed to be autoimmune in origin, mediated by activated T cells which penetrate the blood-brain barrier and attack myelin. The pathophysiology, with respect to function is an impairment of saltatory conduction, specifically, slowing of conduction speed and/or conduction block. Symptoms can temporarily worsen on exposure to heat or during physical exercise. Exercise programmes must be designed to activate working muscles but avoid overload that results in conduction block. Fatigue, often severe, affects about 85% of MS patients and, along with motor and sensory symptoms, results in decreased mobility and reduced quality of life. Physical activity and recreation are reduced in patients with MS. Before developing recommendations, physical activity patterns and the physical effects of MS should be assessed in individual patients. Patients may then be functionally classified. Physical activity can also be classified in a pyramid structure, with the most basic functions forming the base and the most integrated functions on top. The muscular fitness pyramid progresses through passive range of motion, active resistive, specific strengthening and integrated strength exercises Overall physical activity may be increased according to functional level by performing activities of daily living, incorporating inefficiencies into daily living, pursuing more active recreation and eventually developing a structured exercise programme. The importance of the proper exercise environment, balance and coordination issues and factors related to adherence are discussed. PMID:10222541

  2. Peroxidase-like oxidative activity of a manganese-coordinated histidyl bolaamphiphile self-assembly

    NASA Astrophysics Data System (ADS)

    Kim, Min-Chul; Lee, Sang-Yup

    2015-10-01

    A peroxidase-like catalyst was constructed through the self-assembly of histidyl bolaamphiphiles coordinated to Mn2+ ions. The prepared catalyst exhibited oxidation activity for the organic substrate o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2). The histidyl bolaamphiphiles of bis(N-alpha-amido-histidine)-1,7-heptane dicarboxylates self-assembled to make spherical structures in an aqueous solution. Subsequent association of Mn2+ ions with the histidyl imidazoles in the self-assembly produced catalytic active sites. The optimal Mn2+ ion concentration was determined and coordination of the Mn2+ ion with multiple histidine imidazoles was investigated using spectroscopy analysis. The activation energy of the produced catalysts was 55.0 kJ mol-1, which was comparable to other peroxidase-mimetic catalysts. A detailed kinetics study revealed that the prepared catalyst followed a ping-pong mechanism and that the turnover reaction was promoted by increasing the substrate concentration. Finally, application of the prepared catalyst for glucose detection was demonstrated through cascade enzyme catalysis. This study demonstrated a facile way to prepare an enzyme-mimetic catalyst through the self-assembly of an amphiphilic molecule containing amino acid segments.A peroxidase-like catalyst was constructed through the self-assembly of histidyl bolaamphiphiles coordinated to Mn2+ ions. The prepared catalyst exhibited oxidation activity for the organic substrate o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2). The histidyl bolaamphiphiles of bis(N-alpha-amido-histidine)-1,7-heptane dicarboxylates self-assembled to make spherical structures in an aqueous solution. Subsequent association of Mn2+ ions with the histidyl imidazoles in the self-assembly produced catalytic active sites. The optimal Mn2+ ion concentration was determined and coordination of the Mn2+ ion with multiple histidine imidazoles was investigated using spectroscopy

  3. Bacterial Cyclic AMP-Phosphodiesterase Activity Coordinates Biofilm Formation

    PubMed Central

    Kalivoda, Eric J.; Brothers, Kimberly M.; Stella, Nicholas A.; Schmitt, Matthew J.; Shanks, Robert M. Q.

    2013-01-01

    Biofilm-related infections are a major contributor to human disease, and the capacity for surface attachment and biofilm formation are key attributes for the pathogenesis of microbes. Serratia marcescens type I fimbriae-dependent biofilms are coordinated by the adenylate cyclase, CyaA, and the cyclic 3′,5′-adenosine monophosphate (cAMP)-cAMP receptor protein (CRP) complex. This study uses S. marcescens as a model system to test the role of cAMP-phosphodiesterase activity in controlling biofilm formation. Herein we describe the characterization of a putative S. marcescens cAMP-phosphodiesterase gene (SMA3506), designated as cpdS, and demonstrated to be a functional cAMP-phosphodiesterase both in vitro and in vivo. Deletion of cpdS resulted in defective biofilm formation and reduced type I fimbriae production, whereas multicopy expression of cpdS conferred a type I fimbriae-dependent hyper-biofilm. Together, these results support a model in which bacterial cAMP-phosphodiesterase activity modulates biofilm formation. PMID:23923059

  4. First MRI application of an active breathing coordinator

    NASA Astrophysics Data System (ADS)

    Kaza, E.; Symonds-Tayler, R.; Collins, D. J.; McDonald, F.; McNair, H. A.; Scurr, E.; Koh, D.-M.; Leach, M. O.

    2015-02-01

    A commercial active breathing coordinator (ABC) device, employed to hold respiration at a specific level for a predefined duration, was successfully adapted for magnetic resonance imaging (MRI) use for the first time. Potential effects of the necessary modifications were assessed and taken into account. Automatic MR acquisition during ABC breath holding was achieved. The feasibility of MR-ABC thoracic and abdominal examinations together with the advantages of imaging in repeated ABC-controlled breath holds were demonstrated on healthy volunteers. Five lung cancer patients were imaged under MR-ABC, visually confirming the very good intra-session reproducibility of organ position in images acquired with the same patient positioning as used for computed tomography (CT). Using identical ABC settings, good MR-CT inter-modality registration was achieved. This demonstrates the value of ABC, since application of T1, T2 and diffusion weighted MR sequences provides a wider range of contrast mechanisms and additional diagnostic information compared to CT, thus improving radiotherapy treatment planning and assessment.

  5. Motor coordination as predictor of physical activity in childhood.

    PubMed

    Lopes, V P; Rodrigues, L P; Maia, J A R; Malina, R M

    2011-10-01

    This study considers relationships among motor coordination (MC), physical fitness (PF) and physical activity (PA) in children followed longitudinally from 6 to 10 years. It is hypothesized that MC is a significant and primary predictor of PA in children. Subjects were 142 girls and 143 boys. Height, weight and skinfolds; PA (Godin-Shephard questionnaire); MC (Körperkoordination Test für Kinder); and PF (five fitness items) were measured. Hierarchical linear modeling with MC and PF as predictors of PA was used. The retained model indicated that PA at baseline differed significantly between boys (48.3 MET/week) and girls (40.0 MET/week). The interaction of MC and 1 mile run/walk had a positive influence on level of PA. The general trend for a decrease in PA level across years was attenuated or amplified depending on initial level of MC. The estimated rate of decline in PA was negligible for children with higher levels of MC at 6 years, but was augmented by 2.58 and 2.47 units each year, respectively, for children with low and average levels of initial MC. In conclusion MC is an important predictor of PA in children 6-10 years of age.

  6. Photocatalytic activity of PANI loaded coordination polymer composite materials: Photoresponse region extension and quantum yields enhancement via the loading of PANI nanofibers on surface of coordination polymer

    SciTech Connect

    Cui, Zhongping; Qi, Ji; Xu, Xinxin Liu, Lu; Wang, Yi

    2013-09-15

    To enhance photocatalytic property of coordination polymer in visible light region, polyaniline (PANI) loaded coordination polymer photocatalyst was synthesized through in-situ chemical oxidation of aniline on the surface of coordination polymer. The photocatalytic activity of PANI loaded coordination polymer composite material for degradation of Rhodamine B (RhB) was investigated. Compared with pure coordination polymer photocatalyst, which can decompose RhB merely under UV light irradiation, PANI loaded coordination polymer photocatalyst displays more excellent photocatalytic activity in visible light region. Furthermore, PANI loaded coordination polymer photocatalyst exhibits outstanding stability during the degradation of RhB. - Graphical abstract: PANI loaded coordination polymer composite material, which displays excellent photocatalytic activity under visible light was firstly synthesized through in-situ chemical oxidation of aniline on surface of coordination polymer. Display Omitted - Highlights: • This PANI loaded coordination polymer composite material represents the first conductive polymer loaded coordination polymer composite material. • PANI/coordination polymer composite material displays more excellent photocatalytic activity for the degradation of MO in visible light region. • The “combination” of coordination polymer and PANI will enable us to design high-activity, high-stability and visible light driven photocatalyst in the future.

  7. A practical approach for active camera coordination based on a fusion-driven multi-agent system

    NASA Astrophysics Data System (ADS)

    Bustamante, Alvaro Luis; Molina, José M.; Patricio, Miguel A.

    2014-04-01

    In this paper, we propose a multi-agent system architecture to manage spatially distributed active (or pan-tilt-zoom) cameras. Traditional video surveillance algorithms are of no use for active cameras, and we have to look at different approaches. Such multi-sensor surveillance systems have to be designed to solve two related problems: data fusion and coordinated sensor-task management. Generally, architectures proposed for the coordinated operation of multiple cameras are based on the centralisation of management decisions at the fusion centre. However, the existence of intelligent sensors capable of decision making brings with it the possibility of conceiving alternative decentralised architectures. This problem is approached by means of a MAS, integrating data fusion as an integral part of the architecture for distributed coordination purposes. This paper presents the MAS architecture and system agents.

  8. Coordinating the activities of a planner and an execution agent

    NASA Technical Reports Server (NTRS)

    Tate, Austin

    1989-01-01

    A research program was defined that will explore the link between planning and execution systems. A simple scenario was defined in which a very capable off-line planning system interacts with the user and a smaller, less capable, on-line real-time system executing plans and reacting to faults. However, the on-line execution system may have a more flexible representation of the plans it is executing. This imbalance in the capabilities of the two agents involved should clarify some of the research objectives and give an experimental framework for the work. The task is to investigate the knowledge representations and communication protocols needed to link a user stating some requirements for a task to be carried out through a planning system to the (remote) execution agent that can carry out the user's wishes. The notion that a single representation can encapsulate the expression of the user's requirements, the capabilities for action, the communication to the execution agent, the successful or faulty response from the execution agent and the means of keeping the user informed, is examined. Methods of creating plan patches to update the plans separately held by each of the parties involved to keep them in step as they each react to changing circumstances in real-time is investigated. This involves the specification of plan patch attachment points that can be understood by the recipient. Transaction based methods are also investigated for coordinating the activities of the planner with those of the execution agent and user. The trial application area for the research is in the command and control of an advanced Earth Observation Space Platform.

  9. Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanofibers: improved stability and an enzyme cascade for glucose detection.

    PubMed

    Liang, Hao; Jiang, Shuhui; Yuan, Qipeng; Li, Guofeng; Wang, Feng; Zhang, Zijie; Liu, Juewen

    2016-03-21

    Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn(2+) and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules. PMID:26932320

  10. Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanofibers: improved stability and an enzyme cascade for glucose detection.

    PubMed

    Liang, Hao; Jiang, Shuhui; Yuan, Qipeng; Li, Guofeng; Wang, Feng; Zhang, Zijie; Liu, Juewen

    2016-03-21

    Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn(2+) and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules.

  11. BK channels: multiple sensors, one activation gate.

    PubMed

    Yang, Huanghe; Zhang, Guohui; Cui, Jianmin

    2015-01-01

    Ion transport across cell membranes is essential to cell communication and signaling. Passive ion transport is mediated by ion channels, membrane proteins that create ion conducting pores across cell membrane to allow ion flux down electrochemical gradient. Under physiological conditions, majority of ion channel pores are not constitutively open. Instead, structural region(s) within these pores breaks the continuity of the aqueous ion pathway, thereby serves as activation gate(s) to control ions flow in and out. To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate. The sensors of ion channels can be broadly categorized as chemical sensors and physical sensors to respond to chemical (such as neural transmitters, nucleotides and ions) and physical (such as voltage, mechanical force and temperature) signals, respectively. With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level. The voltage and Ca(2+) activated BK channels, a K(+) channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate.

  12. BK channels: multiple sensors, one activation gate

    PubMed Central

    Yang, Huanghe; Zhang, Guohui; Cui, Jianmin

    2015-01-01

    Ion transport across cell membranes is essential to cell communication and signaling. Passive ion transport is mediated by ion channels, membrane proteins that create ion conducting pores across cell membrane to allow ion flux down electrochemical gradient. Under physiological conditions, majority of ion channel pores are not constitutively open. Instead, structural region(s) within these pores breaks the continuity of the aqueous ion pathway, thereby serves as activation gate(s) to control ions flow in and out. To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate. The sensors of ion channels can be broadly categorized as chemical sensors and physical sensors to respond to chemical (such as neural transmitters, nucleotides and ions) and physical (such as voltage, mechanical force and temperature) signals, respectively. With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level. The voltage and Ca2+ activated BK channels, a K+ channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate. PMID:25705194

  13. Summary of Session Activities: Coordination of Environmental Education Projects

    NASA Technical Reports Server (NTRS)

    Keeler, Michael; Mahootian, Farzad

    1995-01-01

    In this session, we address four fundamental questions related to environmental fields with emphasis on education. These are: What are the goals, objectives, and practical opportunities for coordinating our projects? How can we improve awareness of, interest in, access to, and support the products of our work? How can we build relationships between projects for scientific, educational, technical, and programmatic benefit? How can we evaluate the effectiveness of coordination efforts. In this working session, we produced answers to these questions and proposed a structure for future collaboration.

  14. Active head rotations and eye-head coordination

    NASA Technical Reports Server (NTRS)

    Zangemeister, W. H.; Stark, L.

    1981-01-01

    It is pointed out that head movements play an important role in gaze. The interaction between eye and head movements involves both their shared role in directing gaze and the compensatory vestibular ocular reflex. The dynamics of head trajectories are discussed, taking into account the use of parameterization to obtain the peak velocity, peak accelerations, the times of these extrema, and the duration of the movement. Attention is given to the main sequence, neck muscle EMG and details of the head-movement trajectory, types of head model accelerations, the latency of eye and head movement in coordinated gaze, gaze latency as a function of various factors, and coordinated gaze types. Clinical examples of gaze-plane analysis are considered along with the instantaneous change of compensatory eye movement (CEM) gain, and aspects of variability.

  15. Multiple myeloma and physical activity: a scoping review

    PubMed Central

    Smith, Lee; McCourt, Orla; Henrich, Malgorzata; Paton, Bruce; Yong, Kwee; Wardle, Jane; Fisher, Abigail

    2015-01-01

    Objectives Multiple myeloma is the second most common haematological cancer. A growing body of literature is emerging that investigates the role physical activity plays in all stages of multiple myeloma (prevention and survivorship) and to date no attempt has been made to collate and understand this literature. Therefore, this scoping review aims to (1) outline what is already known about physical activity in all stages of multiple myeloma (2) map the literature on physical activity and multiple myeloma and (3) identify future directions for research. Design Scoping Review. Data Sources Searches were carried out in May 2015. Searchers were conducted in PubMed, Web of Science, SPORTdiscus and MEDLINE. Eligibility criteria for selecting studies To be included studies had to report original data, investigate physical activity per se or physical activity correlates and multiple myeloma or smouldering multiple myeloma. Results A total of 19 papers received full screening, 5 of these papers were excluded. This review identified three journal articles relating to the role of physical activity in the prevention of multiple myeloma, nine papers were identified in the treatment of multiple myeloma and two on smouldering multiple myeloma. Conclusions The search identified that the literature surrounding multiple myeloma and physical activity is very limited. We encourage those designing new cohort studies to allow for future assessment of associations between physical activity and onset of multiple myeloma and smouldering multiple myeloma, as well as the potential role that physical activity plays in the progression from smouldering multiple myeloma to multiple myeloma. Second, we encourage the design and investigation of gender and treatment-specific physical activity interventions in patients with multiple myeloma. Finally, we highlight the need for more randomised controlled trials to evaluate the impact of different types, frequencies and intensities of physical activity

  16. Patient- and family-centered care coordination: a framework for integrating care for children and youth across multiple systems.

    PubMed

    2014-05-01

    Understanding a care coordination framework, its functions, and its effects on children and families is critical for patients and families themselves, as well as for pediatricians, pediatric medical subspecialists/surgical specialists, and anyone providing services to children and families. Care coordination is an essential element of a transformed American health care delivery system that emphasizes optimal quality and cost outcomes, addresses family-centered care, and calls for partnership across various settings and communities. High-quality, cost-effective health care requires that the delivery system include elements for the provision of services supporting the coordination of care across settings and professionals. This requirement of supporting coordination of care is generally true for health systems providing care for all children and youth but especially for those with special health care needs. At the foundation of an efficient and effective system of care delivery is the patient-/family-centered medical home. From its inception, the medical home has had care coordination as a core element. In general, optimal outcomes for children and youth, especially those with special health care needs, require interfacing among multiple care systems and individuals, including the following: medical, social, and behavioral professionals; the educational system; payers; medical equipment providers; home care agencies; advocacy groups; needed supportive therapies/services; and families. Coordination of care across settings permits an integration of services that is centered on the comprehensive needs of the patient and family, leading to decreased health care costs, reduction in fragmented care, and improvement in the patient/family experience of care.

  17. How Georgia State University Personnel Viewed the Coordinated Accreditation Visit of Multiple Agencies.

    ERIC Educational Resources Information Center

    Ezell, Joe B.; And Others

    Georgia State University underwent an accreditation visit believed to be unique in postsecondary education. Eleven agencies sent their committees to the campus during one week in May 1977. The evaluators from these agencies totaled 72. The coordinated approach was aimed at reducing the institutional burden by saving time, effort, and money, while…

  18. Stages in Constructing and Coordinating Units Additively and Multiplicatively (Part 1)

    ERIC Educational Resources Information Center

    Ulrich, Catherine

    2015-01-01

    This is the first of a two-part article that presents a theory of unit construction and coordination that underlies radical constructivist empirical studies of student learning ranging from young students' counting strategies to high school students' algebraic reasoning. My explanation starts with the formation of arithmetical units, which presage…

  19. How Students Learn from Multiple Contexts and Definitions: Proper Time as a Coordination Class

    ERIC Educational Resources Information Center

    Levrini, Olivia; diSessa, Andrea A.

    2008-01-01

    This article provides an empirical analysis of a single classroom episode in which students reveal difficulties with the concept of proper time in special relativity but slowly make progress in improving their understanding. The theoretical framework used is "coordination class theory," which is an evolving model of concepts and conceptual change.…

  20. The Multiple Demands of a Tutor Coordinator: How To Balance a Very Split-Personality Job.

    ERIC Educational Resources Information Center

    Thot, Iris Dolores

    The author of this article describes the various aspects of her job as the Modern Language Tutor Coordinator at Santa Monica College. The author writes that, in general, her days consist of wearing a number of different hats each day, including that of budget and payroll administrator, grant writer, tutor screener, tutor trainer, tutor employer,…

  1. Stages in Constructing and Coordinating Units Additively and Multiplicatively (Part 2)

    ERIC Educational Resources Information Center

    Ulrich, Catherine

    2016-01-01

    This is the second of a two-part article that presents a theory of unit construction and coordination that underlies radical constructivist empirical studies of student learning ranging from young students' counting strategies to high school students' algebraic reasoning. In Part I, I discussed the formation of arithmetical units and composite…

  2. Neural-adaptive control of single-master-multiple-slaves teleoperation for coordinated multiple mobile manipulators with time-varying communication delays and input uncertainties.

    PubMed

    Li, Zhijun; Su, Chun-Yi

    2013-09-01

    In this paper, adaptive neural network control is investigated for single-master-multiple-slaves teleoperation in consideration of time delays and input dead-zone uncertainties for multiple mobile manipulators carrying a common object in a cooperative manner. Firstly, concise dynamics of teleoperation systems consisting of a single master robot, multiple coordinated slave robots, and the object are developed in the task space. To handle asymmetric time-varying delays in communication channels and unknown asymmetric input dead zones, the nonlinear dynamics of the teleoperation system are transformed into two subsystems through feedback linearization: local master or slave dynamics including the unknown input dead zones and delayed dynamics for the purpose of synchronization. Then, a model reference neural network control strategy based on linear matrix inequalities (LMI) and adaptive techniques is proposed. The developed control approach ensures that the defined tracking errors converge to zero whereas the coordination internal force errors remain bounded and can be made arbitrarily small. Throughout this paper, stability analysis is performed via explicit Lyapunov techniques under specific LMI conditions. The proposed adaptive neural network control scheme is robust against motion disturbances, parametric uncertainties, time-varying delays, and input dead zones, which is validated by simulation studies.

  3. Neural-adaptive control of single-master-multiple-slaves teleoperation for coordinated multiple mobile manipulators with time-varying communication delays and input uncertainties.

    PubMed

    Li, Zhijun; Su, Chun-Yi

    2013-09-01

    In this paper, adaptive neural network control is investigated for single-master-multiple-slaves teleoperation in consideration of time delays and input dead-zone uncertainties for multiple mobile manipulators carrying a common object in a cooperative manner. Firstly, concise dynamics of teleoperation systems consisting of a single master robot, multiple coordinated slave robots, and the object are developed in the task space. To handle asymmetric time-varying delays in communication channels and unknown asymmetric input dead zones, the nonlinear dynamics of the teleoperation system are transformed into two subsystems through feedback linearization: local master or slave dynamics including the unknown input dead zones and delayed dynamics for the purpose of synchronization. Then, a model reference neural network control strategy based on linear matrix inequalities (LMI) and adaptive techniques is proposed. The developed control approach ensures that the defined tracking errors converge to zero whereas the coordination internal force errors remain bounded and can be made arbitrarily small. Throughout this paper, stability analysis is performed via explicit Lyapunov techniques under specific LMI conditions. The proposed adaptive neural network control scheme is robust against motion disturbances, parametric uncertainties, time-varying delays, and input dead zones, which is validated by simulation studies. PMID:24808577

  4. Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming

    PubMed Central

    Ding, Junjun; Huang, Xin; Shao, Ningyi; Zhou, Hongwei; Lee, Dung-Fang; Faiola, Francesco; Fidalgo, Miguel; Guallar, Diana; Saunders, Arven; Shliaha, Pavel V.; Wang, Hailong; Waghray, Avinash; Papatsenko, Dmitri; Sánchez-Priego, Carlos; Li, Dan; Yuan, Ye; Lemischka, Ihor R.; Shen, Li; Kelley, Kevin; Deng, Haiteng; Shen, Xiaohua; Wang, Jianlong

    2015-01-01

    SUMMARY Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for the core pluripotency factors Oct4, Sox2, and Nanog. In this study, we sought to dissect the molecular control mechanism of SE activity in pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, we identified Tex10 as a key pluripotency factor that plays a functionally significant role in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation at SEs. Tex10 activity is also important for pluripotency and reprogramming in human cells. Our study therefore highlights Tex10 as a core component of the pluripotency network and sheds light on its role in epigenetic control of SE activity for cell fate determination. PMID:25936917

  5. 48 CFR 2452.237-72 - Coordination of data collection activities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... identical information from ten or more public respondents. Coordination of Data Collection Activities (APR... identical information from ten or more public respondents, the Paperwork Reduction Act (44 U.S.C....

  6. GIT2 Acts as a Systems-Level Coordinator of Neurometabolic Activity and Pathophysiological Aging

    PubMed Central

    Martin, Bronwen; Chadwick, Wayne; Janssens, Jonathan; Premont, Richard T.; Schmalzigaug, Robert; Becker, Kevin G.; Lehrmann, Elin; Wood, William H.; Zhang, Yongqing; Siddiqui, Sana; Park, Sung-Soo; Cong, Wei-na; Daimon, Caitlin M.; Maudsley, Stuart

    2016-01-01

    Aging represents one of the most complicated and highly integrated somatic processes. Healthy aging is suggested to rely upon the coherent regulation of hormonal and neuronal communication between the central nervous system and peripheral tissues. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity and therefore likely coordinates multiple systems in the aging process. We previously identified, in hypothalamic and peripheral tissues, the G protein-coupled receptor kinase interacting protein 2 (GIT2) as a stress response and aging regulator. As metabolic status profoundly affects aging trajectories, we investigated the role of GIT2 in regulating metabolic activity. We found that genomic deletion of GIT2 alters hypothalamic transcriptomic signatures related to diabetes and metabolic pathways. Deletion of GIT2 reduced whole animal respiratory exchange ratios away from those related to primary glucose usage for energy homeostasis. GIT2 knockout (GIT2KO) mice demonstrated lower insulin secretion levels, disruption of pancreatic islet beta cell mass, elevated plasma glucose, and insulin resistance. High-dimensionality transcriptomic signatures from islets isolated from GIT2KO mice indicated a disruption of beta cell development. Additionally, GIT2 expression was prematurely elevated in pancreatic and hypothalamic tissues from diabetic-state mice (db/db), compared to age-matched wild type (WT) controls, further supporting the role of GIT2 in metabolic regulation and aging. We also found that the physical interaction of pancreatic GIT2 with the insulin receptor and insulin receptor substrate 2 was diminished in db/db mice compared to WT mice. Therefore, GIT2 appears to exert a multidimensional “keystone” role in regulating the aging process by coordinating somatic responses to energy deficits. PMID:26834700

  7. Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanofibers: improved stability and an enzyme cascade for glucose detection

    NASA Astrophysics Data System (ADS)

    Liang, Hao; Jiang, Shuhui; Yuan, Qipeng; Li, Guofeng; Wang, Feng; Zhang, Zijie; Liu, Juewen

    2016-03-01

    Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn2+ and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules.Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn2+ and adenosine monophosphate (AMP) with a simple mixing step. Most

  8. Coordinated path following of multiple underacutated marine surface vehicles along one curve.

    PubMed

    Liu, Lu; Wang, Dan; Peng, Zhouhua

    2016-09-01

    This paper investigates the coordinated path following problem for a fleet of underactuated marine surface vehicles (MSVs) along one curve. The dedicated control design is divided into two tasks. One is to steer individual underactuated MSV to track the given spatial path, and the other is to force the vehicles dispersed on a parameterized path subject to the constraints of a communication network. Specifically, a robust individual path following controller is developed based on a line-of-sight (LOS) guidance law and a reduced-order extended state observer (ESO). The vehicle sideslip angle due to environmental disturbances can be exactly identified. Then, the vehicle coordination is achieved by a path variable containment approach, under which the path variables are evenly dispersed between two virtual leaders. Another reduced-order ESO is developed to identify the composite disturbance related to the speed of virtual leaders and neighboring vehicles. The proposed coordination design is distributed since the reference speed does not need to be known by all vehicles as a priori. The input-to-state stability of the closed-loop network system is established via cascade theory. Simulation results demonstrate the effectiveness of the proposed design method.

  9. Coordinated path following of multiple underacutated marine surface vehicles along one curve.

    PubMed

    Liu, Lu; Wang, Dan; Peng, Zhouhua

    2016-09-01

    This paper investigates the coordinated path following problem for a fleet of underactuated marine surface vehicles (MSVs) along one curve. The dedicated control design is divided into two tasks. One is to steer individual underactuated MSV to track the given spatial path, and the other is to force the vehicles dispersed on a parameterized path subject to the constraints of a communication network. Specifically, a robust individual path following controller is developed based on a line-of-sight (LOS) guidance law and a reduced-order extended state observer (ESO). The vehicle sideslip angle due to environmental disturbances can be exactly identified. Then, the vehicle coordination is achieved by a path variable containment approach, under which the path variables are evenly dispersed between two virtual leaders. Another reduced-order ESO is developed to identify the composite disturbance related to the speed of virtual leaders and neighboring vehicles. The proposed coordination design is distributed since the reference speed does not need to be known by all vehicles as a priori. The input-to-state stability of the closed-loop network system is established via cascade theory. Simulation results demonstrate the effectiveness of the proposed design method. PMID:27198459

  10. General Relativistic Elastic Body, Fluid,quasi-rigid Body, Quasi-liquid and Others in Multiple Coordinate Systems

    NASA Astrophysics Data System (ADS)

    Xu, Chongming

    2009-05-01

    The approximation method in multiple coordinate systems at first post Newtonian (1 PN) level has been established by Darmour, Soffel and Xu (Phys. Rev. D(PRD) 43, 3273 (1991);D 45, 1017(1992);D 47, 3124 (1993);D 49, 618 (1994)). Normally, to discuss an astronomical object (e.g. a star in binary systems or the earth in solar system) we need multiple coordinate systems, especially for precise astrometry 1 PN (some time even 2 PN) approximate method is required. As we know up to now the ideas on elastic body, fluid, rigid body and liquid in the framework of Newtonian physics are still very useful for understanding and calculating some practical problems. Although the general relativistic theories of elastic body, general relativistic hydrodynamics and post-Newtonian quasi-rigid body have been discussed by many authors (including our papers (PRD63, 043002(2001); D63, 064001(2001); D68, 064009(2003); D69, 024003(2004); D71,024030 (2005))), but there is no completing discussion on all of these ideas in a unified point view. The applications of these ideas in the general relativity are important in the research fields of astrometry and geophysics, especially in case precise measurements reach so higher level (millimicro arc sec). The extended relativistic versions of these ideas should be revised the Newtonian results. In this paper, we shall give a complete discussion on all of these ideas in 1 PN approximation. We shall clarify the ideas on perfect elastic material, quasi-rigid body, quasi-liquid and so on with some precise mathematical forms. For fluid we show the hydrodynamic equations of a non-perfect fluid in multiple coordinates systems (both local and global).

  11. Muscle activity during functional coordination training: implications for strength gain and rehabilitation.

    PubMed

    Jørgensen, Marie B; Andersen, Lars L; Kirk, Niels; Pedersen, Mogens T; Søgaard, Karen; Holtermann, Andreas

    2010-07-01

    The purpose of this study was to evaluate if different types, body positions, and levels of progression of functional coordination exercises can provide sufficiently high levels of muscle activity to improve strength of the neck, shoulder, and trunk muscles. Nine untrained women were familiarized with 7 functional coordination exercises 12 times during 4 weeks before testing. Surface electromyographic (EMG) activity was obtained from rectus abdominus, erector spinae, obliquus externus, and trapezius during the exercises with 2-4 levels of progression. Electromyography was normalized to the maximal EMG activity during maximal voluntary contractions, and a p value < 0.05 was considered significant. All recorded muscles reached sufficiently high levels of activity during the coordination exercises for strength gain (>60% of maximal EMG activity). Type of exercise played a significant role for the attained muscle activity. Body position during the exercises was important for the activity of the erector spinae, and level of progression was important for the activity of the trapezius. The findings indicate that depending on type, body position, and level of progression, functional coordination training can be performed with a muscle activity sufficient for strength gain. Functional coordination training may therefore be a good choice for prevention or rehabilitation of musculoskeletal pain or injury in the neck, shoulder, or trunk muscles.

  12. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... proposed activity will affect any coastal use or resource substantially different than originally described... supporting a finding of substantially different coastal effects than originally described and the...

  13. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... proposed activity will affect any coastal use or resource substantially different than originally described... supporting a finding of substantially different coastal effects than originally described and the...

  14. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... proposed activity will affect any coastal use or resource substantially different than originally described... supporting a finding of substantially different coastal effects than originally described and the...

  15. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... proposed activity will affect any coastal use or resource substantially different than originally described... supporting a finding of substantially different coastal effects than originally described and the...

  16. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... proposed activity will affect any coastal use or resource substantially different than originally described... supporting a finding of substantially different coastal effects than originally described and the...

  17. [History and activities of the Rescue Coordination Center].

    PubMed

    Hausman, A

    1983-01-01

    The founder and first director of the C.C.R. enumerates the principles that led to the conception and the achievement of the C.C.R. He reviews the principal rescue activities during these 25 years and mentions the development of supplementary activities on safety, ergonomics and respiratory protection during the last few years.

  18. Coordinated transporter activity shapes high-affinity iron acquisition in cyanobacteria

    PubMed Central

    Kranzler, Chana; Lis, Hagar; Finkel, Omri M; Schmetterer, Georg; Shaked, Yeala; Keren, Nir

    2014-01-01

    Iron bioavailability limits biological activity in many aquatic and terrestrial environments. Broad scale genomic meta-analyses indicated that within a single organism, multiple iron transporters may contribute to iron acquisition. Here, we present a functional characterization of a cyanobacterial iron transport pathway that utilizes concerted transporter activities. Cyanobacteria are significant contributors to global primary productivity with high iron demands. Certain cyanobacterial species employ a siderophore-mediated uptake strategy; however, many strains possess neither siderophore biosynthesis nor siderophore transport genes. The unicellular, planktonic, freshwater cyanobacterium, Synechocystis sp. PCC 6803, employs an alternative to siderophore-based uptake-reduction of Fe(III) species before transport through the plasma membrane. In this study, we combine short-term radioactive iron uptake and reduction assays with a range of disruption mutants to generate a working model for iron reduction and uptake in Synechocystis sp. PCC 6803. We found that the Fe(II) transporter, FeoB, is the major iron transporter in this organism. In addition, we uncovered a link between a respiratory terminal oxidase (Alternate Respiratory Terminal Oxidase) and iron reduction - suggesting a coupling between these two electron transfer reactions. Furthermore, quantitative RNA transcript analysis identified a function for subunits of the Fe(III) transporter, FutABC, in modulating reductive iron uptake. Collectively, our results provide a molecular basis for a tightly coordinated, high-affinity iron transport system. PMID:24088625

  19. Coordinated ventilation and spiracle activity produce unidirectional airflow in the hissing cockroach, Gromphadorhina portentosa.

    PubMed

    Heinrich, Erica C; McHenry, Matthew J; Bradley, Timothy J

    2013-12-01

    Insects exchange respiratory gases via an extensive network of tracheal vessels that open to the surface of the body through spiracular valves. Although gas exchange is known to increase with the opening of these spiracles, it is not clear how this event relates to gas flow through the tracheal system. We examined the relationship between respiratory airflow and spiracle activity in a ventilating insect, the hissing cockroach, Gromphadorhina portentosa, to better understand the complexity of insect respiratory function. Using simultaneous video recordings of multiple spiracular valves, we found that abdominal spiracles open and close in unison during periods of ventilation. Additionally, independent recordings of CO2 release from the abdominal and thoracic regions and observations of hyperoxic tracer gas movement indicate that air is drawn into the thoracic spiracles and expelled from the abdominal spiracles. Our video recordings suggest that this unidirectional flow is driven by abdominal contractions that occur when the abdominal spiracles open. The spiracles then close as the abdomen relaxes and fills with air from the thorax. Therefore, the respiratory system of the hissing cockroach functions as a unidirectional pump through the coordinated action of the spiracles and abdominal musculature. This mechanism may be employed by a broad diversity of large insects that respire by active ventilation. PMID:24031063

  20. The product of microbial uranium reduction includes multiple species with U(IV)-phosphate coordination

    NASA Astrophysics Data System (ADS)

    Alessi, Daniel S.; Lezama-Pacheco, Juan S.; Stubbs, Joanne E.; Janousch, Markus; Bargar, John R.; Persson, Per; Bernier-Latmani, Rizlan

    2014-04-01

    Until recently, the reduction of U(VI) to U(IV) during bioremediation was assumed to produce solely the sparingly soluble mineral uraninite, UO2(s). However, results from several laboratories reveal other species of U(IV) characterized by the absence of an EXAFS U-U pair correlation (referred to here as noncrystalline U(IV)). Because it lacks the crystalline structure of uraninite, this species is likely to be more labile and susceptible to reoxidation. In the case of single species cultures, analyses of U extended X-ray fine structure (EXAFS) spectra have previously suggested U(IV) coordination to carboxyl, phosphoryl or carbonate groups. In spite of this evidence, little is understood about the species that make up noncrystalline U(IV), their structural chemistry and the nature of the U(IV)-ligand interactions. Here, we use infrared spectroscopy (IR), uranium LIII-edge X-ray absorption spectroscopy (XAS), and phosphorus K-edge XAS analyses to constrain the binding environments of phosphate and uranium associated with Shewanella oneidensis MR-1 bacterial cells. Systems tested as a function of pH included: cells under metal-reducing conditions without uranium, cells under reducing conditions that produced primarily uraninite, and cells under reducing conditions that produced primarily biomass-associated noncrystalline U(IV). P X-ray absorption near-edge structure (XANES) results provided clear and direct evidence of U(IV) coordination to phosphate. Infrared (IR) spectroscopy revealed a pronounced perturbation of phosphate functional groups in the presence of uranium. Analysis of these data provides evidence that U(IV) is coordinated to a range of phosphate species, including monomers and polymerized networks. U EXAFS analyses and a chemical extraction measurements support these conclusions. The results of this study provide new insights into the binding mechanisms of biomass-associated U(IV) species which in turn sheds light on the mechanisms of biological U

  1. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... activities in National Park System units. 9.83 Section 9.83 Parks, Forests, and Public Property NATIONAL PARK... Coordination of AMRAP activities in National Park System units. (a) To facilitate compliance with this Subpart... agreeable schedule of AMRAP projects and activities in Alaska units of the National Park System....

  2. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... activities in National Park System units. 9.83 Section 9.83 Parks, Forests, and Public Property NATIONAL PARK... Coordination of AMRAP activities in National Park System units. (a) To facilitate compliance with this Subpart... agreeable schedule of AMRAP projects and activities in Alaska units of the National Park System....

  3. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... activities in National Park System units. 9.83 Section 9.83 Parks, Forests, and Public Property NATIONAL PARK... Coordination of AMRAP activities in National Park System units. (a) To facilitate compliance with this Subpart... agreeable schedule of AMRAP projects and activities in Alaska units of the National Park System....

  4. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... activities in National Park System units. 9.83 Section 9.83 Parks, Forests, and Public Property NATIONAL PARK... Coordination of AMRAP activities in National Park System units. (a) To facilitate compliance with this Subpart... agreeable schedule of AMRAP projects and activities in Alaska units of the National Park System....

  5. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... activities in National Park System units. 9.83 Section 9.83 Parks, Forests, and Public Property NATIONAL PARK... Coordination of AMRAP activities in National Park System units. (a) To facilitate compliance with this Subpart... agreeable schedule of AMRAP projects and activities in Alaska units of the National Park System....

  6. Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions

    PubMed Central

    Luncsford, Paz J.; Manvilla, Brittney A.; Patterson, Dimeka N.; Malik, Shuja S.; Jin, Jin; Hwang, Bor-Jang; Gunther, Randall; Kalvakolanu, Snigdha; Lipinski, Leonora J.; Yuan, Weirong; Lu, Wuyuan; Drohat, Alexander C.; Lu-Chang, A-Lien; Toth, Eric A.

    2013-01-01

    MutY homologue (MYH) is a DNA glycosylase which excises adenine paired with the oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxoG, or G°) during base excision repair (BER). Base excision by MYH results in an apurinic/apyrimidinic (AP) site in the DNA where the DNA sugar-phosphate backbone remains intact. A key feature of MYH activity is its physical interaction and coordination with AP endonuclease I (APE1), which subsequently nicks DNA 5' to the AP site. Because AP sites are mutagenic and cytotoxic, they must be processed by APE1 immediately after the action of MYH glycosylase. Our recent reports show that the interdomain connector (IDC) of human MYH (hMYH) maintains interactions with hAPE1 and the human checkpoint clamp Rad9-Rad1-Hus1 (9-1-1) complex. In this study, we used NMR chemical shift perturbation experiments to determine hMYH-binding site on hAPE1. Chemical shift perturbations indicate that the hMYH IDC peptide binds to the DNA-binding site of hAPE1 and an additional site which is distal to the APE1 DNA-binding interface. In these two binding sites, N212 and Q137 of hAPE1 are key mediators of the MYH/APE1 interaction. Intriguingly, despite the fact that hHus1 and hAPE1 both interact with the MYH IDC, hHus1 does not compete with hAPE1 for binding to hMYH. Rather, hHus1 stabilizes the hMYH/hAPE1 complex both in vitro and in cells. This is consistent with a common theme in BER, namely that the assembly of protein-DNA complexes enhances repair by efficiently coordinating multiple enzymatic steps while simultaneously minimizing the release of harmful repair intermediates. PMID:24209961

  7. Statistical methods for analysis of coordination of chest wall motion using optical reflectance imaging of multiple markers

    NASA Astrophysics Data System (ADS)

    Kenyon, C. M.; Ghezzo, R. H.; Cala, S. J.; Ferrigno, Giancarlo; Pedotti, Antonio; Macklem, P. T.; Rochester, D. F.

    1994-07-01

    To analyze coordination of chest wall motion we have used principle component analysis (PCA) and multiple regression analysis (MRA) with respect to spirometry on the displacements of 93 optical reflective markers placed upon the chest wall (CW). Each marker is tracked at 10 Hz with an accuracy of 0.2 mm in each spatial dimension using the ELITE system (IEEE Trans. Biomed. Eng. 11:943-949, 1985). PCA enables the degree of linear coordination between all of the markers to be assessed using the eigenvectors and eigenvalues of the covariance of the matrix of marker displacements in each dimension against time. Thus the number of linear degrees of freedom (DOF) which contribute more than a particular amount to the total variance can be determined and analyzed. MRA with respect to spirometrically measured lung volume changes enables identification of the CW points whose movement correlates best with lung volume. We have used this analysis to compare a quiet breathing sequence with one where tidal volume was increased fourfold involuntarily and show that the number of DOF with eigenvalues accounting for >5% of the covariance increased from 2 to 3. Also the point whose movement correlated best with lung volume changed from halfway down the lower costal margin to a more lateral point at the level of the bottom of the sternum. This quantification of CW coordination may be useful in analysis and staging of many respiratory disorders and is applicable to any nonrigid body motion where points can be tracked.

  8. Economy-oriented vehicle adaptive cruise control with coordinating multiple objectives function

    NASA Astrophysics Data System (ADS)

    Eben Li, Shengbo; Li, Keqiang; Wang, Jianqiang

    2013-01-01

    A recent design issue of adaptive cruise control systems is how to reduce fuel consumption when following a preceding vehicle. High fuel economy is achievable through reducing acceleration level, however, it is also significantly restrained by two other functional demands, track capability and driver desired response. In the framework of multi-objective coordination, this paper develops and experimentally validates an economy-oriented headway control algorithm for a passenger car with internal combustion engine. The control algorithm is synthesised in a hierarchical structure. The upper controller, undertaking a major coordinating task, is designed based on the model predictive control theory. Fuel economy, tracking capability, and the driver desired response are formulated as its cost function and constraints in a finite prediction horizon. As further analysis indicated, such a design inevitably results in infeasible control inputs in some extreme cases, e.g. urgent situations involving rapid acceleration/deceleration. A constraint softening method is adopted to enlarge the feasible region in the cost of somewhat sacrificing the optimality of the original cost function. Finally, a prototyping controller is developed based on xPC toolbox and equipped in a passenger car. The followed field tests show that, compared to a linear quadratic controller, such an algorithm improves both fuel economy and tracking capability while also being more responsive to driver car-following behaviours.

  9. Mindfulness-based interventions in multiple sclerosis: beneficial effects of Tai Chi on balance, coordination, fatigue and depression

    PubMed Central

    2014-01-01

    Background Patients suffering from Multiple Sclerosis (MS) experience a wide array of symptoms, including balance problems, mobility impairment, fatigue and depression. Physical exercise has recently been acknowledged as a treatment option complementary to medication. However, information regarding putative effects of structured exercise programs on neurological symptoms is sparse. Tai Chi, a Chinese martial art incorporating physical exercise and mindfulness training, has been shown to yield health benefits in various neurological groups. It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance. The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination, balance, fatigue and depression in mildly disabled MS patients. Methods A sample of 32 MS patients (Expanded Disability Status Scale, EDSS < 5) was examined. A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months, while a comparison group received treatment as usual (TAU). Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue, depression and life satisfaction. Results Following the intervention, the Tai Chi group showed significant, consistent improvements in balance, coordination, and depression, relative to the TAU group (range of effect-sizes: partial η2 = 0.16 – 0.20). Additionally, life satisfaction improved (partial η2 = 0.31). Fatigue deteriorated in the comparison group, whereas it remained relatively stable in the Tai Chi group (partial η2 = 0.24). Conclusions The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients. Further research is needed to determine underlying working mechanisms, and to verify the results in a larger sample and different MS

  10. Coordinating the Effects of Multiple Variables: A Skill Fundamental to Scientific Thinking

    ERIC Educational Resources Information Center

    Kuhn, Deanna; Pease, Maria; Wirkala, Clarice

    2009-01-01

    The skill of predicting outcomes based on simultaneous effects of multiple factors was examined. Over five sessions, 91 sixth graders engaged this task either individually or in pairs and either preceded or followed by six sessions on the more widely studied inquiry task that requires designing and interpreting experiments to identify individual…

  11. Variables associated with patient activation in persons with multiple sclerosis.

    PubMed

    Goodworth, Marie-Christine R; Stepleman, Lara; Hibbard, Judith; Johns, Lisa; Wright, Dustin; Hughes, Mary D; Williams, Mitzi J

    2016-01-01

    Identifying variables associated with patient activation in the multiple sclerosis population could serve to facilitate better multiple sclerosis self-management behaviors. Using a cross-sectional survey design, 199 participants were recruited from a multiple sclerosis center in the Southeastern United States. Depression, multiple sclerosis quality of life, and multiple Sclerosis self-efficacy were all significantly correlated with patient activation. Results of a hierarchical regression indicated that patient activation was significantly related to educational attainment, depression, and self-efficacy but not to quality of life. The results suggest several possible targets for intervention to increase patient activation, including health literacy, depression symptoms, and self-efficacy for multiple sclerosis disease management.

  12. Subcellular and Dynamic Coordination between Src Activity and Cell Protrusion in Microenvironment

    PubMed Central

    Zhuo, Yue; Qian, Tongcheng; Wu, Yiqian; Seong, Jihye; Gong, Ya; Ma, Hongwei; Wang, Yingxiao; Lu, Shaoying

    2015-01-01

    Migration of endothelial cells is essential for wound healing and angiogenesis. Src kinase activity plays important roles at the protrusions of migrating endothelial cells. However, the spatiotemporal coordination between Src kinase activity and the protrusion of cell edge remains unclear. Therefore, we investigate these coordinated molecular events at the initiation of cell migration, by integrating microfabrication, fluorescence resonance energy transfer (FRET)-based biosensors, and automated computational image analysis. We demonstrate that the physical release of restrictive micropattern triggered a significant decrease of Src activity at the protrusive edge of endothelial cells. Computational cross-correlation analysis reveals that the decrease of Src activity occurred earlier in time, and was well-coordinated with the protrusion of cell edge in polarized cells, but not in non-polarized cells. These results suggest that the spatiotemporal control of Src kinase activity is well-coordinated with cell polarization and protrusion in endothelial cells upon the release of physical constraint, as that experienced by endothelial cells sprouting from stiff tumor micro-environment during angiogenesis. Therefore, our integrative approach enabled the discovery of a new model where Src is de-activated in coordination with membrane protrusion, providing important insights into the regulation of endothelial migration and angiogenesis. PMID:26261043

  13. Endocytosis-dependent coordination of multiple actin regulators is required for wound healing.

    PubMed

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla; Millard, Tom H

    2015-08-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form "signaling centers" along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing.

  14. Simulating Activities: Relating Motives, Deliberation and Attentive Coordination

    NASA Technical Reports Server (NTRS)

    Clancey, William J.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Activities are located behaviors, taking time, conceived as socially meaningful, and usually involving interaction with tools and the environment. In modeling human cognition as a form of problem solving (goal-directed search and operator sequencing), cognitive science researchers have not adequately studied "off-task" activities (e.g., waiting), non-intellectual motives (e.g., hunger), sustaining a goal state (e.g., playful interaction), and coupled perceptual-motor dynamics (e.g., following someone). These aspects of human behavior have been considered in bits and pieces in past research, identified as scripts, human factors, behavior settings, ensemble, flow experience, and situated action. More broadly, activity theory provides a comprehensive framework relating motives, goals, and operations. This paper ties these ideas together, using examples from work life in a Canadian High Arctic research station. The emphasis is on simulating human behavior as it naturally occurs, such that "working" is understood as an aspect of living. The result is a synthesis of previously unrelated analytic perspectives and a broader appreciation of the nature of human cognition. Simulating activities in this comprehensive way is useful for understanding work practice, promoting learning, and designing better tools, including human-robot systems.

  15. Coordinated Activities of Human Dicer Domains in Regulatory RNA Processing

    PubMed Central

    Ma, Enbo; Zhou, Kaihong; Kidwell, Mary Anne; Doudna, Jennifer A.

    2012-01-01

    Summary The conserved ribonuclease Dicer generates microRNAs and short interfering RNAs that guide gene silencing in eukaryotes. The specific contributions of human Dicer's structural domains to RNA product length and substrate preference are incompletely understood, due in part to the difficulties of Dicer purification. Here we show that active forms of human Dicer can be assembled from recombinant polypeptides expressed in bacteria. Using this system, we find that three distinct modes of RNA recognition give rise to Dicer's fidelity and product length specificity. The first involves anchoring one end of a dsRNA helix within the PAZ domain, which can assemble in trans with Dicer's catalytic domains to reconstitute an accurate but non-substrate-selective dicing activity. The second entails non-specific RNA binding by the double-stranded RNA binding domain (dsRBD), an interaction that is essential for substrate recruitment in the absence of the PAZ domain. The third mode of recognition involves hairpin RNA loop recognition by the helicase domain, which ensures efficient processing of specific substrates. These results reveal distinct interactions of each Dicer domain with different RNA structural features, and provide a facile system for investigating the molecular mechanisms of human miRNA biogenesis. PMID:22727743

  16. Can Gymnastic Teacher Predict Leisure Activity Preference among Children with Developmental Coordination Disorders (DCD)?

    ERIC Educational Resources Information Center

    Engel-Yeger, Batya; Hanna-Kassis, Amany; Rosenblum, Sara

    2012-01-01

    The aims of the study were to analyze: (1) whether significant differences exist between children with typical development and children with developmental coordination disorders (DCD) in their preference to participate in leisure activities (2) whether the teacher estimation of activity form (TEAF) evaluation predicts participation preference.…

  17. Comparing Activity Patterns, Biological, and Family Factors in Children with and without Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Beutum, Monique Natalie; Cordier, Reinie; Bundy, Anita

    2013-01-01

    The association between motor proficiency and moderate to vigorous physical activity (MVPA) suggests children with developmental coordination disorder (DCD) may be susceptible to inactivity-related conditions such as cardiovascular diseases. The aim of this study was to compare children with and without DCD on physical activity patterns, activity…

  18. Physical Activity and Fitness in Children with Developmental Coordination Disorder: A Systematic Review

    ERIC Educational Resources Information Center

    Rivilis, Irina; Hay, John; Cairney, John; Klentrou, Panagiota; Liu, Jian; Faught, Brent E.

    2011-01-01

    Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by poor motor proficiency that interferes with a child's activities of daily living. Activities that most young children engage in such as running, walking, and jumping are important for the proper development of fitness and overall health. However, children…

  19. Rapid and enhanced activation of microporous coordination polymers by flowing supercritical CO.sub.2

    DOEpatents

    Matzger, Adam J.; Liu, Baojian; Wong-Foy, Antek G.

    2016-07-19

    Flowing supercritical CO.sub.2 is used to activate metal organic framework materials (MOF). MOFs are activated directly from N,N-dimethylformamide (DMF) thus avoiding exchange with a volatile solvent. Most MCPs display increased surface areas directly after treatment although those with coordinatively unsaturated metal centers benefit from additional heating.

  20. Rrp5 Binding at Multiple Sites Coordinates Pre-rRNA Processing and Assembly

    PubMed Central

    Lebaron, Simon; Segerstolpe, Åsa; French, Sarah L.; Dudnakova, Tatiana; de lima Alves, Flavia; Granneman, Sander; Rappsilber, Juri; Beyer, Ann L.; Wieslander, Lars; Tollervey, David

    2013-01-01

    Summary In vivo UV crosslinking identified numerous preribosomal RNA (pre-rRNA) binding sites for the large, highly conserved ribosome synthesis factor Rrp5. Intramolecular complementation has shown that the C-terminal domain (CTD) of Rrp5 is required for pre-rRNA cleavage at sites A0–A2 on the pathway of 18S rRNA synthesis, whereas the N-terminal domain (NTD) is required for A3 cleavage on the pathway of 5.8S/25S rRNA synthesis. The CTD was crosslinked to sequences flanking A2 and to the snoRNAs U3, U14, snR30, and snR10, which are required for cleavage at A0–A2. The NTD was crosslinked to sequences flanking A3 and to the RNA component of ribonuclease MRP, which cleaves site A3. Rrp5 could also be directly crosslinked to several large structural proteins and nucleoside triphosphatases. A key role in coordinating preribosomal assembly and processing was confirmed by chromatin spreads. Following depletion of Rrp5, cotranscriptional cleavage was lost and preribosome compaction greatly reduced. PMID:24239293

  1. Making Sense of Multiple Physical Activity Recommendations.

    ERIC Educational Resources Information Center

    Corbin, Charles B.; LeMasurier, Guy; Franks, B. Don

    2002-01-01

    This digest provides basic information designed to help people determine which of the many physical activity guidelines are most appropriate for use in specific situations. After an introduction, the digest focuses on: "Factors to Consider in Selecting Appropriate Physical Activity Guidelines" (group credibility and purpose, benefits to be…

  2. Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

    PubMed Central

    de Wiljes, Oltman O.; van Elburg, Ronald A. J.; Biehl, Michael; Keijzer, Fred A.

    2015-01-01

    Internal coordination models hold that early nervous systems evolved in the first place to coordinate internal activity at a multicellular level, most notably the use of multicellular contractility as an effector for motility. A recent example of such a model, the skin brain thesis, suggests that excitable epithelia using chemical signaling are a potential candidate as a nervous system precursor. We developed a computational model and a measure for whole body coordination to investigate the coordinative properties of such excitable epithelia. Using this measure we show that excitable epithelia can spontaneously exhibit body-scale patterns of activation. Relevant factors determining the extent of patterning are the noise level for exocytosis, relative body dimensions, and body size. In smaller bodies whole-body coordination emerges from cellular excitability and bidirectional excitatory transmission alone. Our results show that basic internal coordination as proposed by the skin brain thesis could have arisen in this potential nervous system precursor, supporting that this configuration may have played a role as a proto-neural system and requires further investigation. PMID:26441620

  3. Computer coordination of limb motion for locomotion of a multiple-armed robot for space assembly

    NASA Technical Reports Server (NTRS)

    Klein, C. A.; Patterson, M. R.

    1982-01-01

    Consideration is given to a possible robotic system for the construction of large space structures, which may be described as a multiple general purpose arm manipulator vehicle that can walk over the structure under construction to a given site for further work. A description is presented of the locomotion of such a vehicle, modeling its arms in terms of a currently available industrial manipulator. It is noted that for whatever maximum speed of operation is chosen, rapid changes in robot velocity create situations in which already-selected handholds are no longer practical. A step is added to the 'free gait' walking algorithm in order to solve this problem.

  4. Brain activity mapping at multiple scales with silicon microprobes containing 1,024 electrodes

    PubMed Central

    Shobe, Justin L.; Claar, Leslie D.; Parhami, Sepideh; Bakhurin, Konstantin I.

    2015-01-01

    The coordinated activity of neural ensembles across multiple interconnected regions has been challenging to study in the mammalian brain with cellular resolution using conventional recording tools. For instance, neural systems regulating learned behaviors often encompass multiple distinct structures that span the brain. To address this challenge we developed a three-dimensional (3D) silicon microprobe capable of simultaneously measuring extracellular spike and local field potential activity from 1,024 electrodes. The microprobe geometry can be precisely configured during assembly to target virtually any combination of four spatially distinct neuroanatomical planes. Here we report on the operation of such a device built for high-throughput monitoring of neural signals in the orbitofrontal cortex and several nuclei in the basal ganglia. We perform analysis on systems-level dynamics and correlations during periods of conditioned behavioral responding and rest, demonstrating the technology's ability to reveal functional organization at multiple scales in parallel in the mouse brain. PMID:26133801

  5. Multiple-robot drug delivery strategy through coordinated teams of microswimmers

    SciTech Connect

    Kei Cheang, U; Kim, Min Jun; Lee, Kyoungwoo; Julius, Anak Agung

    2014-08-25

    Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.

  6. Multiple-robot drug delivery strategy through coordinated teams of microswimmers

    NASA Astrophysics Data System (ADS)

    Kei Cheang, U.; Lee, Kyoungwoo; Julius, Anak Agung; Kim, Min Jun

    2014-08-01

    Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.

  7. Catalytic activity of unsaturated coordinated Cu-MOF to the hydroxylation of phenol

    NASA Astrophysics Data System (ADS)

    Jian, Lijuan; Chen, Chao; Lan, Fan; Deng, Shengjun; Xiao, Weiming; Zhang, Ning

    2011-05-01

    A 2D metal-organic framework [Cu 2 (BPTC) (Im) 4(H 2O) (DMF)] n ( 1) with unsaturated coordinated Cu(II) sites has been prepared under solvothermal condition, and applied to the hydroxylation of phenol after activating. The catalytic results indicate that 1a (the activated 1) exhibits an obvious activity for phenol hydroxylation at 40 °C for 4 h. Compared to the control experiments where the free Cu(II) (from Cu(OAc) 2 salt) has been utilized as the catalysts, 1a shows the higher selectivity to diphenols. This suggests that the coordinated environment of unsaturated coordinated Cu(II) sites in the 2D layer play the key role in the phenol hydroxylation.

  8. Supramolecular coordination and antimicrobial activities of constructed mixed ligand complexes

    NASA Astrophysics Data System (ADS)

    El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Abou-Dobara, M. I.; Seyam, H. A.

    2013-03-01

    A novel series of copper(II) and palladium(II) with 4-derivatives benzaldehyde pyrazolone (Ln) were synthesized. The mixed ligand complexes were prepared by using 1,10-phenanthroline (Phen) as second ligand. The structure of these complexes was identified and confirm by elemental analysis, molar conductivity, UV-Vis, IR and 1H NMR spectroscopy and magnetic moment measurements as well as thermal analysis. The ligand behaves as a neutral bidentate ligand through ON donor sites. ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in the 1:2 ratio for all N,O complexes [Cu(Ln)2]Cl2ṡ2H2O. Schiff bases (Ln) were tested against bacterial species; namely two Gram positive bacteria (Staphylococcus aureus and Bacillus cereus) and two Gram negative bacteria (Escherichia coli and Klebsiella pneumoniae) and fungal species (Aspergillus niger, Fusarium oxysporium, Penicillium italicum and Alternaria alternata). The tested compounds have antibacterial activity against S. aureus, B. cereus and K. pneumoniae.

  9. Coordination and conformational isomers in mononuclear iron complexes with pertinence to the [FeFe] hydrogenase active site.

    PubMed

    Orthaber, Andreas; Karnahl, Michael; Tschierlei, Stefanie; Streich, Daniel; Stein, Matthias; Ott, Sascha

    2014-03-21

    A series of six mononuclear iron complexes of the type [Fe(X-bdt)(P(R)2N(Ph)2)(CO)] (P(R)2N(Ph)2 = 1,5-diaza-3,7-diphosphaoctane, bdt = benzenedithiolate with X = H, Cl2 or Me and R = Ph, Bn, Cyc or tert-Bu) was prepared. This new class of penta-coordinate iron complexes contains a free coordination site and a pendant base as essential structural features of the [FeFe]-hydrogenase active site. The bidentate nature of the P(R)2N(Ph)2 ligands was found to be crucial for the preferential formation of coordinatively unsaturated penta-coordinate complexes, which is supported by first principle calculations. IR-spectroscopic data suggest the presence of coordination isomers around the metal center, as well as multiple possible conformers of the P(R)2N(Ph)2 ligand. This finding is further corroborated by X-ray crystallographic and computational studies. (31)P{(1)H}-NMR- and IR-spectroscopic as well as electrochemical measurements show that the electronic properties of the complexes are strongly, and independently, influenced by the P-substituents at the P(R)2N(Ph)2 ligand as well as by modifications of the bdt bridge. These results illustrate the advantages of this modular platform, which allows independent and selective tuning through site specific modifications. Potential catalytic intermediates, namely singly reduced and protonated complexes, have been further investigated by spectroscopic methods and exhibit remarkable stability. Finally, their general capacity for electro-catalytic reduction of protons to molecular hydrogen was verified.

  10. 'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

    PubMed

    Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

    2014-04-01

    The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

  11. Biomechanical Characteristics of Hand Coordination in Grasping Activities of Daily Living

    PubMed Central

    Liu, Ming-Jin; Xiong, Cai-Hua; Xiong, Le; Huang, Xiao-Lin

    2016-01-01

    Hand coordination can allow humans to have dexterous control with many degrees of freedom to perform various tasks in daily living. An important contributing factor to this important ability is the complex biomechanical architecture of the human hand. However, drawing a clear functional link between biomechanical architecture and hand coordination is challenging. It is not understood which biomechanical characteristics are responsible for hand coordination and what specific effect each biomechanical characteristic has. To explore this link, we first inspected the characteristics of hand coordination during daily tasks through a statistical analysis of the kinematic data, which were collected from thirty right-handed subjects during a multitude of grasping tasks. Then, the functional link between biomechanical architecture and hand coordination was drawn by establishing the clear corresponding causality between the tendinous connective characteristics of the human hand and the coordinated characteristics during daily grasping activities. The explicit functional link indicates that the biomechanical characteristic of tendinous connective architecture between muscles and articulations is the proper design by the Creator to perform a multitude of daily tasks in a comfortable way. The clear link between the structure and the function of the human hand also suggests that the design of a multifunctional robotic hand should be able to better imitate such basic architecture. PMID:26730579

  12. Multiple objective optimization for active sensor management

    NASA Astrophysics Data System (ADS)

    Page, Scott F.; Dolia, Alexander N.; Harris, Chris J.; White, Neil M.

    2005-03-01

    The performance of a multi-sensor data fusion system is inherently constrained by the configuration of the given sensor suite. Intelligent or adaptive control of sensor resources has been shown to offer improved fusion performance in many applications. Common approaches to sensor management select sensor observation tasks that are optimal in terms of a measure of information. However, optimising for information alone is inherently sub-optimal as it does not take account of any other system requirements such as stealth or sensor power conservation. We discuss the issues relating to developing a suite of performance metrics for optimising multi-sensor systems and propose some candidate metrics. In addition it may not always be necessary to maximize information gain, in some cases small increases in information gain may take place at the cost of large sensor resource requirements. Additionally, the problems of sensor tasking and placement are usually treated separately, leading to a lack of coherency between sensor management frameworks. We propose a novel approach based on a high level decentralized information-theoretic sensor management architecture that unifies the processes of sensor tasking and sensor placement into a single framework. Sensors are controlled using a minimax multiple objective optimisation approach in order to address probability of target detection, sensor power consumption, and sensor survivability whilst maintaining a target estimation covariance threshold. We demonstrate the potential of the approach through simulation of a multi-sensor, target tracking scenario and compare the results with a single objective information based approach.

  13. Soluble porous coordination polymers by mechanochemistry: from metal-containing films/membranes to active catalysts for aerobic oxidation.

    PubMed

    Zhang, Pengfei; Li, Haiying; Veith, Gabriel M; Dai, Sheng

    2015-01-14

    Soluble porous coordination polymers from mechanochemical synthesis are presented through a coordination polymerization between highly contorted, rigid tetraphenol and a broad variety of transition metal ions. These polymers can be easily cast as metal-containing films or freestanding membranes. Importantly, as-made coordination polymers are highly active and stable in the aerobic oxidation of allylic C-H bonds. PMID:25389070

  14. Co-ordination of contractile activity in guinea-pig mesenteric lymphatics.

    PubMed Central

    Crowe, M J; von der Weid, P Y; Brock, J A; Van Helden, D F

    1997-01-01

    1. Intraluminally perfused lymphatic vessels from the mesentery of the guinea-pig were examined in vitro to investigate their contractile activity and the co-ordination of this activity between adjacent lymphangions. 2. Lymphangions constricted at fairly regular intervals and exhibited 'refractory' periods of up to 3 s during which constrictions did not occur. 3. The contractile activity of adjacent lymphangions was highly co-ordinated. 4. The smooth muscle was found to be continuous between the adjacent lymphangions for the majority of valve regions examined morphologically (52 of 63 preparations). 5. Mechanical and electrical coupling between adjacent lymphangions was indicated, as some lymphangions underwent transient dilatations just prior to constriction, whereas direct electrophysiological measurements showed that the smooth muscle of most adjacent lymphangions was electrically coupled across the valve (15 out of 20 pairs of lymphangions). 6. It is concluded that perfused lymphangions of guinea-pig mesenteric lymphatic vessels rhythmically constrict, with the contractile activity of adjacent lymphangions highly co-ordinated. The findings also indicate that transmission of both mechanical and electrical signals between the adjacent lymphangions contribute to the co-ordination of their contractile activity. Images Figure 4 PMID:9097947

  15. Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells

    NASA Astrophysics Data System (ADS)

    Kiyonaka, Shigeki; Kubota, Ryou; Michibata, Yukiko; Sakakura, Masayoshi; Takahashi, Hideo; Numata, Tomohiro; Inoue, Ryuji; Yuzaki, Michisuke; Hamachi, Itaru

    2016-10-01

    The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2‧-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway.

  16. Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells.

    PubMed

    Kiyonaka, Shigeki; Kubota, Ryou; Michibata, Yukiko; Sakakura, Masayoshi; Takahashi, Hideo; Numata, Tomohiro; Inoue, Ryuji; Yuzaki, Michisuke; Hamachi, Itaru

    2016-10-01

    The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2'-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway. PMID:27657873

  17. Fungal proteinaceous compounds with multiple biological activities.

    PubMed

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Yau Sang; Dan, Xiuli; Pan, Wenliang; Wang, Hexiang; Guan, Suzhen; Chan, Ki; Ye, Xiuyun; Liu, Fang; Xia, Lixin; Chan, Wai Yee

    2016-08-01

    Fungi comprise organisms like molds, yeasts and mushrooms. They have been used as food or medicine for a long time. A large number of fungal proteins or peptides with diverse biological activities are considered as antibacterial, antifungal, antiviral and anticancer agents. They encompass proteases, ribosome inactivating proteins, defensins, hemolysins, lectins, laccases, ribonucleases, immunomodulatory proteins, and polysaccharopeptides. The target of the present review is to update the status of the various bioactivities of these fungal proteins and peptides and discuss their therapeutic potential. PMID:27338574

  18. Active control of multiple resistive wall modes

    NASA Astrophysics Data System (ADS)

    Brunsell, P. R.; Yadikin, D.; Gregoratto, D.; Paccagnella, R.; Liu, Y. Q.; Bolzonella, T.; Cecconello, M.; Drake, J. R.; Kuldkepp, M.; Manduchi, G.; Marchiori, G.; Marrelli, L.; Martin, P.; Menmuir, S.; Ortolani, S.; Rachlew, E.; Spizzo, G.; Zanca, P.

    2005-12-01

    A two-dimensional array of saddle coils at Mc poloidal and Nc toroidal positions is used on the EXTRAP T2R reversed-field pinch (Brunsell P R et al 2001 Plasma Phys. Control. Fusion 43 1457) to study active control of resistive wall modes (RWMs). Spontaneous growth of several RWMs with poloidal mode number m = 1 and different toroidal mode number n is observed experimentally, in agreement with linear MHD modelling. The measured plasma response to a controlled coil field and the plasma response computed using the linear circular cylinder MHD model are in quantitive agreement. Feedback control introduces a linear coupling of modes with toroidal mode numbers n, n' that fulfil the condition |n - n'| = Nc. Pairs of coupled unstable RWMs are present in feedback experiments with an array of Mc × Nc = 4 × 16 coils. Using intelligent shell feedback, the coupled modes are generally not controlled even though the field is suppressed at the active coils. A better suppression of coupled modes may be achieved in the case of rotating modes by using the mode control feedback scheme with individually set complex gains. In feedback with a larger array of Mc × Nc = 4 × 32 coils, the coupling effect largely disappears, and with this array, the main internal RWMs n = -11, -10, +5, +6 are all simultaneously suppressed throughout the discharge (7 8 wall times). With feedback there is a two-fold extension of the pulse length, compared to discharges without feedback.

  19. A barium based coordination polymer for the activity assay of deoxyribonuclease I.

    PubMed

    Song, Chan; Wang, Guan-Yao; Wang, Ya-Ling; Kong, De-Ming; Wang, Yong-Jian; Li, Yue; Ruan, Wen-Juan

    2014-10-01

    A new coordination polymer which shows an unusual 2D inorganic connectivity was constructed. This compound exhibits distinct fluorescence quenching ability to the dye-labeled single-stranded DNA probes with different lengths, based on which an analytical method was developed for the activity assay of deoxyribonuclease I.

  20. Developmental Coordination Disorder, Gender, and Body Weight: Examining the Impact of Participation in Active Play

    ERIC Educational Resources Information Center

    Cairney, John; Kwan, Matthew Y. W.; Hay, John A.; Faught, Brent E.

    2012-01-01

    Background: To examine whether differences in participation in active play (PAP) can account for gender differences in the relationship between Developmental Coordination Disorder (DCD) and body weight/fat (BMI and percentage fat) in youth. Methods: A cross-sectional investigation of students in grades four through eight (n = 590). Height, weight…

  1. 3 CFR - Designation of the National Science and Technology Council to Coordinate Certain Activities Under...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 3 The President 1 2011-01-01 2011-01-01 false Designation of the National Science and Technology Council to Coordinate Certain Activities Under the Arctic Research and Policy Act of 1984 Presidential Documents Other Presidential Documents Memorandum of July 22, 2010 Designation of the National Science...

  2. Physical activity, physical fitness, gross motor coordination, and metabolic syndrome: focus of twin research in Portugal.

    PubMed

    Maia, José António Ribeiro; Santos, Daniel; de Freitas, Duarte Luis; Thomis, Martine

    2013-02-01

    A very brief history of Portuguese twin research in sport and human movement sciences is presented. Recruitment procedures, zygosity determination, and phenotypes are given for twins and their parents from the mainland, and Azores and Madeira archipelagos. Preliminary findings are mostly related to physical activity, health-related physical fitness, gross motor coordination, neuromotor development, and metabolic syndrome traits.

  3. State Research Coordinating Unit Activities for the Period July 1, 1971-December 31, 1971. Semiannual Report.

    ERIC Educational Resources Information Center

    Bureau of Adult, Vocational, and Technical Education (DHEW/OE), Washington, DC.

    This semiannual report summarizes research activities of the State Research Coordinating Units conducted under Section 131(b) of the Vocational Education Amendments of 1968 during the first half of fiscal year 1972. The purpose of the report is to facilitate exchange of information and reduce duplication of effort among the states by providing…

  4. Analysis of initial in-plant active neutron multiplicity measurements

    SciTech Connect

    Ensslin, N.; Krick, M.S.; Harker, W.C.

    1993-08-01

    This paper analyzes initial in-plant measurements made by active neutron multiplicity counting, a new technique currently under development for the assay of bulk uranium containing kilograms of {sup 235}U. The measurements were made at Savannah River and Y-12 using active well coincidence counters and prototype multiplicity electronics and software from Los Alamos. For one of the sets of highly enriched uranium samples measured to data, we improved the assay accuracy by an order-of-magnitude by adding the multiplicity analysis to the conventional coincidence analysis. This paper summarizes our results and describes areas where further work is needed.

  5. Multiple Wavelength Observations of Flaring Active Regions

    NASA Astrophysics Data System (ADS)

    Lang, Kenneth R.

    The radio emission of quiescent active regions at 6 cm wavelength marks the legs of magnetic dipoles, and the emission at 20 cm wavelength delineates the radio wavelength counterpart of the coronal loops previously detected at X-ray wavelengths. At both wavelengths the temperatures have coronal values of a few million degrees. The polarization of the radio emission specifies the structure and strength of the coronal magnetic field (H ≈ 600 Gauss at heights h ≈ 4 x 109 cm above sunspot umbrae). At 6 cm and 20 cm wavelength the solar bursts have angular sizes between 5" and 30", brightness temperatures between 2 x 107 K and 2 x 108 K, and degrees of circular polarization between 10% and 90%. The location of the burst energy release is specified with second-of-arc accuracy. At radio wavelengths the bursts occur within the central regions of magnetic loops, while the flaring Ha kernels are located at the loop footpoints. Coronal loops exhibit enhanced radio emission (preburst heating) a few minutes before the release of burst energy. The radio polarization data indicate magnetic changes before and during solar bursts.

  6. Developmental Coordination Disorder, Sex, and Activity Deficit over Time: A Longitudinal Analysis of Participation Trajectories in Children with and without Coordination Difficulties

    ERIC Educational Resources Information Center

    Cairney, John; Hay, John A.; Veldhuizen, Scott; Missiuna, Cheryl; Faught, Brent E.

    2010-01-01

    Aim: Children with developmental coordination disorder (DCD) are known to participate in active play less than typically developing children. However, it is not known whether the activity deficit between children with and without DCD widens or diminishes over time. Method: Data were obtained from a large, prospective cohort study of children…

  7. Coordination number of zinc ions in the phosphotriesterase active site by molecular dynamics and quantum mechanics.

    PubMed

    Koca, Jaroslav; Zhan, Chang-Guo; Rittenhouse, Robert C; Ornstein, Rick L

    2003-02-01

    We have run several molecular dynamics (MD) simulations on zinc-containing phosphotriesterase (PTE) with two bound substrates, sarin and paraoxon, and with the substrate analog diethyl 4-methylbenzylphosphonate. A standard nonbonded model was employed to treat the zinc ions with the commonly used charge of +2. In all the trajectories, we observed a tightly bound water (TBW) molecule in the active site that was coordinated to the less buried zinc ion. The phosphoryl oxygen of the substrate/inhibitor was found to be coordinated to the same zinc ion so that, considering all ligands, the less buried zinc was hexa-coordinated. The hexa-coordination of this zinc ion was not seen in the deposited X-ray pdb files for PTE. Several additional MD simulations were then performed using different charges (+1, +1.5) on the zinc ions, along with ab initio and density functional theory (DFT) calculations, to evaluate the following possibilities: the crystal diffraction data were not correctly interpreted; the hexa-coordinated zinc ion in PTE is only present in solution and not in the crystal; and the hexa-coordinated zinc ion in PTE is an artifact of the force field used. A charge of +1.5 leads to a coordination number (CN) of 5 on both zinc ions, which is consistent with the results from ab initio and DFT calculations and with the latest high resolution X-ray crystal structure. The commonly used charge of +2 produces a CN of 6 on the less buried zinc. The CN on the more buried zinc ion is 5 when the substrate/inhibitor is present in the simulation, and increases to 6 when the substrate/inhibitor is removed prior to the simulation. The results of both of the MD and quantum mechanical calculations lead to the conclusion that the zinc ions in the PTE active site are both penta-coordinated, and that the MD simulations performed with the charge of +2 overestimate the CN of the zinc ions in the PTE active site. The overall protein structures in the simulations remain unaffected by the

  8. Chitosan-Copper (II) complex as antibacterial agent: synthesis, characterization and coordinating bond- activity correlation study

    NASA Astrophysics Data System (ADS)

    Mekahlia, S.; Bouzid, B.

    2009-11-01

    The antimicrobial activity of chitosan is unstable and sensitive to many factors such as molecular weight. Recent investigations showed that low molecular weight chitosan exhibited strong bactericidal activities compared to chitosan with high molecular weight. Since chitosan degradation can be caused by the coordinating bond, we attempt to synthesize and characterize the chitosan-Cu (II) complex, and thereafter study the coordinating bond effect on its antibacterial activity against Salmonella enteritidis. Seven chitosan-copper complexes with different copper contents were prepared and characterized by FT-IR, UV-vis, XRD and atomic absorption spectrophotometry (AAS). Results indicated that for chitosan-Cu (II) complexes with molar ratio close to 1:1, the inhibition rate reached 100%.

  9. Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.

    PubMed

    Wang, Junjian; Duan, Zhijian; Nugent, Zoann; Zou, June X; Borowsky, Alexander D; Zhang, Yanhong; Tepper, Clifford G; Li, Jian Jian; Fiehn, Oliver; Xu, Jianzhen; Kung, Hsing-Jien; Murphy, Leigh C; Chen, Hong-Wu

    2016-08-10

    Metabolic reprogramming such as the aerobic glycolysis or Warburg effect is well recognized as a common feature of tumorigenesis. However, molecular mechanisms underlying metabolic alterations for tumor therapeutic resistance are poorly understood. Through gene expression profiling analysis we found that histone H3K36 methyltransferase NSD2/MMSET/WHSC1 expression was highly elevated in tamoxifen-resistant breast cancer cell lines and clinical tumors. IHC analysis indicated that NSD2 protein overexpression was associated with the disease recurrence and poor survival. Ectopic expression of NSD2 wild type, but not the methylase-defective mutant, drove endocrine resistance in multiple cell models and xenograft tumors. Mechanistically, NSD2 was recruited to and methylated H3K36me2 at the promoters of key glucose metabolic enzyme genes. Its overexpression coordinately up-regulated hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD), two key enzymes of glycolysis and the pentose phosphate pathway (PPP), as well as TP53-induced glycolysis regulatory phosphatase TIGAR. Consequently, NSD2-driven tamoxifen-resistant cells and tumors displayed heightened PPP activity, elevated NADPH production, and reduced ROS level, without significantly altered glycolysis. These results illustrate a coordinated, epigenetic activation of key glucose metabolic enzymes in therapeutic resistance and nominate methyltransferase NSD2 as a potential therapeutic target for endocrine resistant breast cancer.

  10. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures.

    PubMed

    Kaufman, Brett A; Durisic, Nela; Mativetsky, Jeffrey M; Costantino, Santiago; Hancock, Mark A; Grutter, Peter; Shoubridge, Eric A

    2007-09-01

    Packaging DNA into condensed structures is integral to the transmission of genomes. The mammalian mitochondrial genome (mtDNA) is a high copy, maternally inherited genome in which mutations cause a variety of multisystem disorders. In all eukaryotic cells, multiple mtDNAs are packaged with protein into spheroid bodies called nucleoids, which are the fundamental units of mtDNA segregation. The mechanism of nucleoid formation, however, remains unknown. Here, we show that the mitochondrial transcription factor TFAM, an abundant and highly conserved High Mobility Group box protein, binds DNA cooperatively with nanomolar affinity as a homodimer and that it is capable of coordinating and fully compacting several DNA molecules together to form spheroid structures. We use noncontact atomic force microscopy, which achieves near cryo-electron microscope resolution, to reveal the structural details of protein-DNA compaction intermediates. The formation of these complexes involves the bending of the DNA backbone, and DNA loop formation, followed by the filling in of proximal available DNA sites until the DNA is compacted. These results indicate that TFAM alone is sufficient to organize mitochondrial chromatin and provide a mechanism for nucleoid formation.

  11. Photodynamics in stable complexes composed of a zinc porphyrin tripod and pyridyl porphyrins assembled by multiple coordination bonds.

    PubMed

    Takai, Atsuro; Gros, Claude P; Barbe, Jean-Michel; Fukuzumi, Shunichi

    2010-10-14

    A tripod zinc porphyrin (TPZn(3)) forms a stable 1:1 complex with gold(III) tetra(4-pyridyl)porphyrin (AuTPyP(+)) and free-base tris(4-pyridyl)porphyrin (2H-Py(3)P) in nonpolar solvents. The strong binding of TPZn(3) with AuTPyP(+) or 2H-Py(3)P results from the encapsulation of AuTPyP(+) or 2H-Py(3)P inside the cavity of TPZn(3) through multiple coordination bonds, as indicated by UV-vis-NIR, ESI-MS, (1)H NMR, electrochemistry and computational studies. The binding constants of monomer zinc porphyrin (MPZn) with AuTPyP(+) and 2H-Py(3)P drastically decrease as compared with TPZn(3). Detailed photophysical studies have been carried out on these composites using laser flash photolysis as well as emission spectroscopy. The efficient quenching of the singlet excited state of TPZn(3) occurs via a photoinduced electron-transfer pathway in the TPZn(3)-AuTPyP(+) complex. In contrast, energy transfer occurs in the TPZn(3)-2H-Py(3)P complex due to the smaller driving force of the photoinduced electron-transfer pathway. Neither electron transfer nor energy transfer occurs from MPZn to AuTPyP(+) under the same experimental conditions due to the small association constant of the monomer zinc porphyrin. PMID:20714588

  12. (S)-2-Amino-6-nitrohexanoic Acid Binds to Human Arginase I through Multiple Nitro−Metal Coordination Interactions in the Binuclear Manganese Cluster

    SciTech Connect

    Zakharian, T.; Di Costanzo, L; Christianson, D

    2008-01-01

    The binding affinity of (S)-2-amino-6-nitrohexanoic acid to human arginase I was studied using surface plasmon resonance (K{sub d} = 60 {mu}M), and the X-ray crystal structure of the enzyme-inhibitor complex was determined at 1.6 {angstrom} resolution to reveal multiple nitro-metal coordination interactions.

  13. Automatic generation of active coordinates for quantum dynamics calculations: Application to the dynamics of benzene photochemistry

    SciTech Connect

    Lasorne, Benjamin; Sicilia, Fabrizio; Bearpark, Michael J.; Robb, Michael A.; Worth, Graham A.; Blancafort, Lluis

    2008-03-28

    A new practical method to generate a subspace of active coordinates for quantum dynamics calculations is presented. These reduced coordinates are obtained as the normal modes of an analytical quadratic representation of the energy difference between excited and ground states within the complete active space self-consistent field method. At the Franck-Condon point, the largest negative eigenvalues of this Hessian correspond to the photoactive modes: those that reduce the energy difference and lead to the conical intersection; eigenvalues close to 0 correspond to bath modes, while modes with large positive eigenvalues are photoinactive vibrations, which increase the energy difference. The efficacy of quantum dynamics run in the subspace of the photoactive modes is illustrated with the photochemistry of benzene, where theoretical simulations are designed to assist optimal control experiments.

  14. Twinning in fcc lattice creates low-coordinated catalytically active sites in porous gold.

    PubMed

    Krajčí, Marian; Kameoka, Satoshi; Tsai, An-Pang

    2016-08-28

    We describe a new mechanism for creation of catalytically active sites in porous gold. Samples of porous gold prepared by de-alloying Al2Au exhibit a clear correlation between the catalytic reactivity towards CO oxidation and structural defects in the fcc lattice of Au. We have found that on the stepped {211} surfaces quite common twin boundary defects in the bulk structure of porous gold can form long close-packed rows of atoms with the coordination number CN = 6. DFT calculations confirm that on these low-coordinated Au sites dioxygen chemisorbs and CO oxidation can proceed via the Langmuir-Hinshelwood mechanism with the activation energy of 37 kJ/mol or via the CO-OO intermediate with the energy barrier of 19 kJ/mol. The existence of the twins in porous gold is stabilized by the surface energy.

  15. Twinning in fcc lattice creates low-coordinated catalytically active sites in porous gold

    NASA Astrophysics Data System (ADS)

    Krajčí, Marian; Kameoka, Satoshi; Tsai, An-Pang

    2016-08-01

    We describe a new mechanism for creation of catalytically active sites in porous gold. Samples of porous gold prepared by de-alloying Al2Au exhibit a clear correlation between the catalytic reactivity towards CO oxidation and structural defects in the fcc lattice of Au. We have found that on the stepped {211} surfaces quite common twin boundary defects in the bulk structure of porous gold can form long close-packed rows of atoms with the coordination number CN = 6. DFT calculations confirm that on these low-coordinated Au sites dioxygen chemisorbs and CO oxidation can proceed via the Langmuir-Hinshelwood mechanism with the activation energy of 37 kJ/mol or via the CO-OO intermediate with the energy barrier of 19 kJ/mol. The existence of the twins in porous gold is stabilized by the surface energy.

  16. Twinning in fcc lattice creates low-coordinated catalytically active sites in porous gold.

    PubMed

    Krajčí, Marian; Kameoka, Satoshi; Tsai, An-Pang

    2016-08-28

    We describe a new mechanism for creation of catalytically active sites in porous gold. Samples of porous gold prepared by de-alloying Al2Au exhibit a clear correlation between the catalytic reactivity towards CO oxidation and structural defects in the fcc lattice of Au. We have found that on the stepped {211} surfaces quite common twin boundary defects in the bulk structure of porous gold can form long close-packed rows of atoms with the coordination number CN = 6. DFT calculations confirm that on these low-coordinated Au sites dioxygen chemisorbs and CO oxidation can proceed via the Langmuir-Hinshelwood mechanism with the activation energy of 37 kJ/mol or via the CO-OO intermediate with the energy barrier of 19 kJ/mol. The existence of the twins in porous gold is stabilized by the surface energy. PMID:27586937

  17. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal-nitrogen coordination

    NASA Astrophysics Data System (ADS)

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-06-01

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon-nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation.

  18. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal-nitrogen coordination.

    PubMed

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-06-10

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon-nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation.

  19. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal-nitrogen coordination.

    PubMed

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-01-01

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon-nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation. PMID:26059552

  20. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal–nitrogen coordination

    PubMed Central

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-01-01

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon–nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation. PMID:26059552

  1. Sensory integration and activities of daily living in children with developmental coordination disorder

    PubMed Central

    2012-01-01

    Objective The aim of our study was to evaluate sensory integration and activities of daily living in children with developmental coordination disorder Subjects and methods 37 cases with developmental coordination disorder and 35 healthy age-matched peers were included in this study. Ayres Southern California Sensory Integration Test was used for evaluating the sensory integration and Functional Independence Measure for Children (WeeFIM) was used for evaluating the activities of daily living. Results Significant differences were found in the visual shape perception, position in space, and design copying (p < 0.05). According to the results of somatosensory perception tests, significant differences were found in kinesthesia, manual form perception, finger identification, figure-ground perception, localization of tactile stimuli, double tactile stimuli perception (p < 0.05). Control group was better in motor planning (p < 0.05). Comprehension, expression, social communication, problem solving, and memory skills were significant in favor of the control group (p < 0.05). Graphestesia and self-care domain was found to be correlated (r = 0,491, p = 0.002) between the groups. Discussion Special education and rehabilitation programs including sensory integration therapy and motor performance will increase independence in the activities of daily living in children with developmental coordination disorder. PMID:22546072

  2. Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo

    PubMed Central

    Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L.; Dawid, Igor B.

    2009-01-01

    Summary We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation. PMID:19793890

  3. Fabrication of a PANI/CPs composite material: a feasible method to enhance the photocatalytic activity of coordination polymers.

    PubMed

    Xu, Xin-Xin; Cui, Zhong-Ping; Qi, Ji; Liu, Xiao-Xia

    2013-03-21

    To improve the photocatalytic activity of a coordination polymer in the visible light region, polyaniline (PANI) was loaded onto its surface through a facile in situ chemical oxidation polymerization process. The resulting PANI loaded coordination polymer composite materials with excellent stability exhibit significantly higher photocatalytic activities than the pure coordination polymer photocatalyst on the degradation of methyl orange (MO) under visible light irradiation. This enhancement can be ascribed to the introduction of PANI on the surface of the coordination polymer, which leads to efficient separation of photogenerated electron-hole pairs as well as a significant expansion of the photoresponse region. Finally, we discussed the influence of acidity on the morphology and photocatalytic activity of the composite material. An optimal condition to obtain the PANI loaded coordination polymer composite material with excellent photocatalytic activity has been obtained.

  4. Integrating Multiple Space Ground Sensors to Track Volcanic Activity

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Davies, Ashley; Doubleday, Joshua; Tran, Daniel; Jones, Samuel; Kjartansson, Einar; Thorsteinsson, Hrobjartur; Vogfjord, Kristin; Guomundsson, Magnus; Thordarson, Thor; Mandl, Daniel

    2011-01-01

    Volcanic activity can occur with little or no warning. Increasing numbers of space borne assets can enable coordinated measurements of volcanic events to enhance both scientific study and hazard response. We describe the use of space and ground measurements to target further measurements as part of a worldwide volcano monitoring system. We utilize a number of alert systems including the MODVOLC, GOESVOLC, US Air Force Weather Advisory, and Volcanic Ash Advisory Center (VAAC) alert systems. Additionally we use in-situ data from ground instrumentation at a number of volcanic sites, including Iceland.

  5. Multiple strategies to activate gold nanoparticles as antibiotics.

    PubMed

    Zhao, Yuyun; Jiang, Xingyu

    2013-09-21

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  6. Multiple strategies to activate gold nanoparticles as antibiotics

    NASA Astrophysics Data System (ADS)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  7. Physical Activities for Children with Severe Multiple Impairments.

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    1981-01-01

    Intended for teachers of students with severe multiple impairments, the booklet examines the role of physical activities in the education of this population and suggests approaches to exhancing their motor development. Suggestions are offered for stimulating movement in preschool, elementary, and secondary immobile children, including tactile…

  8. An Alternative Method for Analyzing Active Multiplicity Data.

    SciTech Connect

    Pickrell, M. M.

    2005-01-01

    The authors have developed a novel method for analyzing active neutron multiplicity data. The conventional method was derived from the standard passive multiplicity equations known as the point model. The approach was to substitute a term consisting of the product of the interrogation source strength, the coupling coefficient, and the sample mass for the product term of the sample mass and the fission rate: I{kappa}{sub c}m {yields} F{sub 0}m, where I is the source strength, {kappa}{sub c} is the coupling coefficient, m is the sample mass and F is the fission rate. Note that the sample mass, m, refers to the fissile material (e.g. {sup 235}U) in the active case and fertile material (e.g. {sup 240}Pu{sub eff}) in the passive case. In addition, the spontaneous fission multiplicity coefficients, {nu}{sub s}, were replaced with the induced fission multiplicity coefficients, {nu}{sub i}. This model has several drawbacks. The most significant is that the coupling coefficient, {kappa}{sub c}, varies significantly with the multiplication. As a consequence, there is not a clear linear relationship between the doubles rate and the sample mass, nor is there a clear linear relationship between the multiplication-corrected doubles rate and the sample mass. This problem has limited the application of active neutron multiplicity counting. They propose here a novel approach to deriving the multiplicity equations. A different substitution is made in the point model equations. The value of alpha is replaced with a new term, alpha-prime: {alpha} {yields} {alpha}{prime} {triple_bond} {alpha} + {kappa}{sub p}I/Fm{sub 0}{nu}{sub s1}. There are several benefits to this approach, but most significant is that the new coupling coefficient, {kappa}{sub p}, remains constant. In this paper they will establish the general physics justification why this different substitution is appropriate. They will derive the new point model equations for active neutron multiplicity starting from the original

  9. Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation

    PubMed Central

    Cruz-Aceves, I.; Avina-Cervantes, J. G.; Lopez-Hernandez, J. M.; Rostro-Gonzalez, H.; Garcia-Capulin, C. H.; Torres-Cisneros, M.; Guzman-Cabrera, R.

    2013-01-01

    This paper presents a new image segmentation method based on multiple active contours guided by differential evolution, called MACDE. The segmentation method uses differential evolution over a polar coordinate system to increase the exploration and exploitation capabilities regarding the classical active contour model. To evaluate the performance of the proposed method, a set of synthetic images with complex objects, Gaussian noise, and deep concavities is introduced. Subsequently, MACDE is applied on datasets of sequential computed tomography and magnetic resonance images which contain the human heart and the human left ventricle, respectively. Finally, to obtain a quantitative and qualitative evaluation of the medical image segmentations compared to regions outlined by experts, a set of distance and similarity metrics has been adopted. According to the experimental results, MACDE outperforms the classical active contour model and the interactive Tseng method in terms of efficiency and robustness for obtaining the optimal control points and attains a high accuracy segmentation. PMID:23983809

  10. Network activity-independent coordinated gene expression program for synapse assembly

    PubMed Central

    Valor, Luis M.; Charlesworth, Paul; Humphreys, Lawrence; Anderson, Chris N. G.; Grant, Seth G. N.

    2007-01-01

    Global biological datasets generated by genomics, transcriptomics, and proteomics provide new approaches to understanding the relationship between the genome and the synapse. Combined transcriptome analysis and multielectrode recordings of neuronal network activity were used in mouse embryonic primary neuronal cultures to examine synapse formation and activity-dependent gene regulation. Evidence for a coordinated gene expression program for assembly of synapses was observed in the expression of 642 genes encoding postsynaptic and plasticity proteins. This synaptogenesis gene expression program preceded protein expression of synapse markers and onset of spiking activity. Continued expression was followed by maturation of morphology and electrical neuronal networks, which was then followed by the expression of activity-dependent genes. Thus, two distinct sequentially active gene expression programs underlie the genomic programs of synapse function. PMID:17360580

  11. Synthesis, structural characterization and microbial activity of 2D Ag(I)-5-aminoisophthalate coordination polymer with a new coordination mode

    NASA Astrophysics Data System (ADS)

    Günay, Handan; Çolak, Alper Tolga; Yeşilel, Okan Zafer; Tunç, Tuncay; Çolak, Ferdağ

    2015-11-01

    In this study, a novel polynuclear Ag(I)-5-aminoisophthalate complex [Ag(μ4-Haip)]n (1) (H2aip = 5-aminoisophthalic acid) has been synthesized. The molecular structure of this complex has been determined by the single crystal X-ray diffraction. The two-dimensional polynuclear complex is crystallized in the triclinic crystal system with space group P-1. The Ag(I) ion is four-coordinated by three carboxylate oxygen atoms of three different Haip ligands and one nitrogen atom in a distorted tetrahedral geometry. Furthermore, a novel coordination mode has shown by H2aip. This complex exhibits photoluminescence in the solid state at room temperature. Antimicrobial activity of complex was evaluated by the agar diffusion method. The complex showed antimicrobial activity against tested microorganism strains (Gram positive, gram negative bacteria, clinic isolate yeast and mold). Moreover this complex showed particularly high antifungal activity against yeast and mold.

  12. 20 CFR 641.335 - How should the Governor address the coordination of SCSEP services with activities funded under...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... coordination of SCSEP services with activities funded under title I of WIA? 641.335 Section 641.335 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM The State Senior Employment Services Coordination Plan § 641.335...

  13. Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription

    PubMed Central

    Banyai, Gabor; Baïdi, Feriel; Coudreuse, Damien; Szilagyi, Zsolt

    2016-01-01

    Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression. PMID:27045731

  14. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

    PubMed

    Jiménez-Fernández, Alicia; López-Sánchez, Aroa; Jiménez-Díaz, Lorena; Navarrete, Blanca; Calero, Patricia; Platero, Ana Isabel; Govantes, Fernando

    2016-01-01

    Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.

  15. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida

    PubMed Central

    Jiménez-Fernández, Alicia; López-Sánchez, Aroa; Jiménez-Díaz, Lorena; Navarrete, Blanca; Calero, Patricia; Platero, Ana Isabel

    2016-01-01

    Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels. PMID:27636892

  16. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

    PubMed

    Jiménez-Fernández, Alicia; López-Sánchez, Aroa; Jiménez-Díaz, Lorena; Navarrete, Blanca; Calero, Patricia; Platero, Ana Isabel; Govantes, Fernando

    2016-01-01

    Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels. PMID:27636892

  17. Shared Investment Projects and Forecasting Errors: Setting Framework Conditions for Coordination and Sequencing Data Quality Activities

    PubMed Central

    Leitner, Stephan; Brauneis, Alexander; Rausch, Alexandra

    2015-01-01

    In this paper, we investigate the impact of inaccurate forecasting on the coordination of distributed investment decisions. In particular, by setting up a computational multi-agent model of a stylized firm, we investigate the case of investment opportunities that are mutually carried out by organizational departments. The forecasts of concern pertain to the initial amount of money necessary to launch and operate an investment opportunity, to the expected intertemporal distribution of cash flows, and the departments’ efficiency in operating the investment opportunity at hand. We propose a budget allocation mechanism for coordinating such distributed decisions The paper provides guidance on how to set framework conditions, in terms of the number of investment opportunities considered in one round of funding and the number of departments operating one investment opportunity, so that the coordination mechanism is highly robust to forecasting errors. Furthermore, we show that—in some setups—a certain extent of misforecasting is desirable from the firm’s point of view as it supports the achievement of the corporate objective of value maximization. We then address the question of how to improve forecasting quality in the best possible way, and provide policy advice on how to sequence activities for improving forecasting quality so that the robustness of the coordination mechanism to errors increases in the best possible way. At the same time, we show that wrong decisions regarding the sequencing can lead to a decrease in robustness. Finally, we conduct a comprehensive sensitivity analysis and prove that—in particular for relatively good forecasters—most of our results are robust to changes in setting the parameters of our multi-agent simulation model. PMID:25803736

  18. Shared investment projects and forecasting errors: setting framework conditions for coordination and sequencing data quality activities.

    PubMed

    Leitner, Stephan; Brauneis, Alexander; Rausch, Alexandra

    2015-01-01

    In this paper, we investigate the impact of inaccurate forecasting on the coordination of distributed investment decisions. In particular, by setting up a computational multi-agent model of a stylized firm, we investigate the case of investment opportunities that are mutually carried out by organizational departments. The forecasts of concern pertain to the initial amount of money necessary to launch and operate an investment opportunity, to the expected intertemporal distribution of cash flows, and the departments' efficiency in operating the investment opportunity at hand. We propose a budget allocation mechanism for coordinating such distributed decisions The paper provides guidance on how to set framework conditions, in terms of the number of investment opportunities considered in one round of funding and the number of departments operating one investment opportunity, so that the coordination mechanism is highly robust to forecasting errors. Furthermore, we show that-in some setups-a certain extent of misforecasting is desirable from the firm's point of view as it supports the achievement of the corporate objective of value maximization. We then address the question of how to improve forecasting quality in the best possible way, and provide policy advice on how to sequence activities for improving forecasting quality so that the robustness of the coordination mechanism to errors increases in the best possible way. At the same time, we show that wrong decisions regarding the sequencing can lead to a decrease in robustness. Finally, we conduct a comprehensive sensitivity analysis and prove that-in particular for relatively good forecasters-most of our results are robust to changes in setting the parameters of our multi-agent simulation model. PMID:25803736

  19. Shared investment projects and forecasting errors: setting framework conditions for coordination and sequencing data quality activities.

    PubMed

    Leitner, Stephan; Brauneis, Alexander; Rausch, Alexandra

    2015-01-01

    In this paper, we investigate the impact of inaccurate forecasting on the coordination of distributed investment decisions. In particular, by setting up a computational multi-agent model of a stylized firm, we investigate the case of investment opportunities that are mutually carried out by organizational departments. The forecasts of concern pertain to the initial amount of money necessary to launch and operate an investment opportunity, to the expected intertemporal distribution of cash flows, and the departments' efficiency in operating the investment opportunity at hand. We propose a budget allocation mechanism for coordinating such distributed decisions The paper provides guidance on how to set framework conditions, in terms of the number of investment opportunities considered in one round of funding and the number of departments operating one investment opportunity, so that the coordination mechanism is highly robust to forecasting errors. Furthermore, we show that-in some setups-a certain extent of misforecasting is desirable from the firm's point of view as it supports the achievement of the corporate objective of value maximization. We then address the question of how to improve forecasting quality in the best possible way, and provide policy advice on how to sequence activities for improving forecasting quality so that the robustness of the coordination mechanism to errors increases in the best possible way. At the same time, we show that wrong decisions regarding the sequencing can lead to a decrease in robustness. Finally, we conduct a comprehensive sensitivity analysis and prove that-in particular for relatively good forecasters-most of our results are robust to changes in setting the parameters of our multi-agent simulation model.

  20. Embryo as an active granular fluid: stress-coordinated cellular constriction chains

    NASA Astrophysics Data System (ADS)

    Gao, Guo-Jie Jason; Holcomb, Michael C.; Thomas, Jeffrey H.; Blawzdziewicz, Jerzy

    2016-10-01

    Mechanical stress plays an intricate role in gene expression in individual cells and sculpting of developing tissues. However, systematic methods of studying how mechanical stress and feedback help to harmonize cellular activities within a tissue have yet to be developed. Motivated by our observation of the cellular constriction chains (CCCs) during the initial phase of ventral furrow formation in the Drosophila melanogaster embryo, we propose an active granular fluid (AGF) model that provides valuable insights into cellular coordination in the apical constriction process. In our model, cells are treated as circular particles connected by a predefined force network, and they undergo a random constriction process in which the particle constriction probability P is a function of the stress exerted on the particle by its neighbors. We find that when P favors tensile stress, constricted particles tend to form chain-like structures. In contrast, constricted particles tend to form compact clusters when P favors compression. A remarkable similarity of constricted-particle chains and CCCs observed in vivo provides indirect evidence that tensile-stress feedback coordinates the apical constriction activity. Our particle-based AGF model will be useful in analyzing mechanical feedback effects in a wide variety of morphogenesis and organogenesis phenomena.

  1. Embryo as an active granular fluid: stress-coordinated cellular constriction chains.

    PubMed

    Jason Gao, Guo-Jie; Holcomb, Michael C; Thomas, Jeffrey H; Blawzdziewicz, Jerzy

    2016-10-19

    Mechanical stress plays an intricate role in gene expression in individual cells and sculpting of developing tissues. However, systematic methods of studying how mechanical stress and feedback help to harmonize cellular activities within a tissue have yet to be developed. Motivated by our observation of the cellular constriction chains (CCCs) during the initial phase of ventral furrow formation in the Drosophila melanogaster embryo, we propose an active granular fluid (AGF) model that provides valuable insights into cellular coordination in the apical constriction process. In our model, cells are treated as circular particles connected by a predefined force network, and they undergo a random constriction process in which the particle constriction probability P is a function of the stress exerted on the particle by its neighbors. We find that when P favors tensile stress, constricted particles tend to form chain-like structures. In contrast, constricted particles tend to form compact clusters when P favors compression. A remarkable similarity of constricted-particle chains and CCCs observed in vivo provides indirect evidence that tensile-stress feedback coordinates the apical constriction activity. Our particle-based AGF model will be useful in analyzing mechanical feedback effects in a wide variety of morphogenesis and organogenesis phenomena. PMID:27545101

  2. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity

    PubMed Central

    Tigaret, Cezar M.; Olivo, Valeria; Sadowski, Josef H.L.P.; Ashby, Michael C.; Mellor, Jack R.

    2016-01-01

    At glutamatergic synapses, induction of associative synaptic plasticity requires time-correlated presynaptic and postsynaptic spikes to activate postsynaptic NMDA receptors (NMDARs). The magnitudes of the ensuing Ca2+ transients within dendritic spines are thought to determine the amplitude and direction of synaptic change. In contrast, we show that at mature hippocampal Schaffer collateral synapses the magnitudes of Ca2+ transients during plasticity induction do not match this rule. Indeed, LTP induced by time-correlated pre- and postsynaptic spikes instead requires the sequential activation of NMDARs followed by voltage-sensitive Ca2+ channels within dendritic spines. Furthermore, LTP requires inhibition of SK channels by mGluR1, which removes a negative feedback loop that constitutively regulates NMDARs. Therefore, rather than being controlled simply by the magnitude of the postsynaptic calcium rise, LTP induction requires the coordinated activation of distinct sources of Ca2+ and mGluR1-dependent facilitation of NMDAR function. PMID:26758963

  3. Multiple LREK active contours for knee meniscus ultrasound image segmentation.

    PubMed

    Faisal, Amir; Ng, Siew-Cheok; Goh, Siew-Li; George, John; Supriyanto, Eko; Lai, Khin W

    2015-10-01

    Quantification of knee meniscus degeneration and displacement in an ultrasound image requires simultaneous segmentation of femoral condyle, meniscus, and tibial plateau in order to determine the area and the position of the meniscus. In this paper, we present an active contour for image segmentation that uses scalable local regional information on expandable kernel (LREK). It includes using a strategy to adapt the size of a local window in order to avoid being confined locally in a homogeneous region during the segmentation process. We also provide a multiple active contours framework called multiple LREK (MLREK) to deal with multiple object segmentation without merging and overlapping between the neighboring contours in the shared boundaries of separate regions. We compare its performance to other existing active contour models and show an improvement offered by our model. We then investigate the choice of various parameters in the proposed framework in response to the segmentation outcome. Dice coefficient and Hausdorff distance measures over a set of real knee meniscus ultrasound images indicate a potential application of MLREK for assessment of knee meniscus degeneration and displacement. PMID:25910057

  4. SATB1 packages densely-looped, transciptionally-active chromatinfor coordinated expression of cytokine genes

    SciTech Connect

    Cai, Shutao; Lee, Charles C.; Kohwi-Shigematsu, Terumi

    2006-05-23

    SATB1 is an important regulator of nuclear architecture that anchors specialized DNA sequences onto its cage-like network and recruits chromatin remodeling/modifying factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4, and Il13 from the 200kb cytokine gene cluster region of mouse chromosome 11 during T-helper 2 (Th2)-cell activation. We show that upon cell activation, SATB1 is rapidly induced to form a unique transcriptionally-active chromatin structure that includes the cytokine gene region. Chromatin is folded into numerous small loops all anchored by SATB1, is histone H3 acetylated at lysine 9/14, and associated with Th2-specific factors, GATA3, STAT6, c-Maf, the chromatin-remodeling enzyme Brg-1, and RNA polymerase II across the 200kb region. Before activation, the chromatin displays some of these features, such as association with GATA3 and STAT6, but these were insufficient for cytokine gene expression. Using RNA interference (RNAi), we show that upon cell activation, SATB1 is not only required for chromatin folding into dense loops, but also for c-Maf induction and subsequently for Il4, Il5, and Il13 transcription. Our results show that SATB1 is an important determinant for chromatin architecture that constitutes a novel higher-order, transcriptionally-active chromatin structure upon Th2-cell activation.

  5. Difference in Activity in the Supplementary Motor Area Depending on Limb Combination of Hand–Foot Coordinated Movements

    PubMed Central

    Nakagawa, Kento; Kawashima, Saeko; Mizuguchi, Nobuaki; Kanosue, Kazuyuki

    2016-01-01

    Periodic interlimb coordination shows lower performance when the ipsilateral hand and foot (e.g., right hand and right foot) are simultaneously moved than when the contralateral hand and foot (e.g., right hand and left foot) are simultaneously moved. The present study aimed to investigate how brain activity that is related to the dependence of hand–foot coordination on limb combination, using functional magnetic imaging. Twenty-one right-handed subjects performed periodic coordinated movements of the ipsilateral or contralateral hand and foot in the same or opposite direction in the sagittal plane. Kinematic data showed that performance was lower for the ipsilateral hand–foot coordination than for the contralateral one. A comparison of brain activity between the same and opposite directions showed that there was a greater activation of supplementary motor area for ipsilateral hand–foot coordination as compared to that seen during contralateral hand–foot coordination. We speculate that this might reflect a difference in the degree of inhibition of the neural circuit that disrupts opposite directional movements between ipsilateral and contralateral hand–foot coordinated movements. PMID:27757079

  6. Loading of a coordination polymer nanobelt on a functional carbon fiber: a feasible strategy for visible-light-active and highly efficient coordination-polymer-based photocatalysts.

    PubMed

    Xu, Xin-Xin; Yang, Hong-Yu; Li, Zhen-Yu; Liu, Xiao-Xia; Wang, Xiu-Li

    2015-02-23

    To improve the photocatalytic properties of coordination polymers under irradiation in the visible-light region, coordination polymer nanobelts (CPNB) were loaded on functional carbon fiber (FCF) through the use of a simple colloidal blending process. The resulting coordination polymer nanobelt loaded functional carbon fiber composite material (CPNB/FCF) exhibited dramatically improved photocatalytic activity for the degradation of rhodamine B (RhB) under visible-light irradiation. Optical and electrochemical methods illustrated the enhanced photocatalytic activity of CPNB/FCF originated from high separation efficiency of photogenerated electrons and holes on the interface of CPNB and FCF, which was produced by the synergy effect between them. In the composite material, the role of FCF could be described as photosensitizer and good electron transporter. For FCF, the number of functional groups on its surface has a significant influence on the photocatalytic performance of the resulting CPNB/FCF composite material, and an ideal FCF carrier was obtained as a highly efficient CPNB/FCF photocatalyst. CPNB/FCF showed outstanding stability during the degradation of rhodamine B (RhB); thus, the material is suitable for use as a photocatalyst in the treatment of organic dyes in water.

  7. Transition Metal Ions in Zeolites: Coordination and activation of O2

    PubMed Central

    Smeets, Pieter J.; Woertink, Julia S.; Sels, Bert F.; Solomon, Edward I.; Schoonheydt, Robert A.

    2010-01-01

    Zeolites containing transition metal ions (TMI) often show promising activity as heterogeneous catalysts in pollution abatement and selective oxidation reactions. In this paper, two aspects of research on the TMI Cu, Co and Fe in zeolites are discussed: (i) coordination to the lattice and (ii) activated oxygen species. At low loading, TMI preferably occupy exchange sites in six-membered oxygen rings (6MR) where the TMI preferentially coordinate with the oxygen atoms of Al tetrahedra. High TMI loadings result in a variety of TMI species formed at the zeolite surface. Removal of the extra-lattice oxygens during high temperature pretreatments can result in auto-reduction. Oxidation of reduced TMI sites often results in the formation of highly reactive oxygen species. In Cu-ZSM-5, calcination with O2 results in the formation of a species, which was found to be a crucial intermediate in both the direct decomposition of NO and N2O and the selective oxidation of methane into methanol. An activated oxygen species, called α-oxygen, is formed in Fe-ZSM5 and reported to be the active site in the partial oxidation of methane and benzene into methanol and phenol, respectively. However, this reactive α-oxygen can only be formed with N2O, not with O2. O2 activated Co intermediates in Faujasite (FAU) zeolites can selectively oxidize α-pinene and epoxidize styrene. In Co-FAU, CoIII superoxo and peroxo complexes are suggested to be the active cores, whereas in Cu and Fe-ZSM-5 various monomeric and dimeric sites have been proposed, but no consensus has been obtained. Very recently, the active site in Cu-ZSM-5 was identified as a bent [Cu-O-Cu]2+ core (Proc. Natl. Acad. Sci. USA 2009, 106, 18908-18913). Overall, O2 activation depends on the interplay of structural factors such as type of zeolite, size of the channels and cages and chemical factors such as Si/Al ratio and the nature, charge and distribution of the charge balancing cations. The presence of several different TMI sites

  8. Coordinated Action of Fast and Slow Reserves for Optimal Sequential and Dynamic Emergency Reserve Activation

    NASA Astrophysics Data System (ADS)

    Salkuti, Surender Reddy; Bijwe, P. R.; Abhyankar, A. R.

    2016-04-01

    This paper proposes an optimal dynamic reserve activation plan after the occurrence of an emergency situation (generator/transmission line outage, load increase or both). An optimal plan is developed to handle the emergency situation, using coordinated action of fast and slow reserves, for secure operation with minimum overall cost. This paper considers the reserves supplied by generators (spinning reserves) and loads (demand-side reserves). The optimal backing down of costly/fast reserves and bringing up of slow reserves in each sub-interval in an integrated manner is proposed. The simulation studies are performed on IEEE 30, 57 and 300 bus test systems to demonstrate the advantage of proposed integrated/dynamic reserve activation plan over the conventional/sequential approach.

  9. Normal coordinate analysis and fungicidal activity study on anilazine and its related compound using spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Sheeja Mol, Gilbert Pushpam; Arul Dhas, Deva Dhas; Hubert Joe, Isaac; Balachandran, Sreedharan

    2016-06-01

    The FTIR and FT-Raman spectra of anilazine have been recorded in the range 400-4000 cm-1 and 50-3500 cm-1 respectively. The optimized geometrical parameters of the compound were calculated using B3LYP method with 6-311G(d,p) basis set. The distribution of the vibrational bands were carried out with the help of normal coordinate analysis (NCA). The 1H and 13C nuclear spectra have been recorded and chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method. The UV-Visible spectrum of the compound was recorded in the region 190-900 nm and the electronic properties were determined by time-dependent DFT (TD-DFT) approach. Anilazine was screened for its antifungal activity. Molecular docking studies are conducted to predict its fungicidal activity.

  10. Decipher the dynamic coordination between enzymatic activity and structural modulation at focal adhesions in living cells

    NASA Astrophysics Data System (ADS)

    Lu, Shaoying; Seong, Jihye; Wang, Yi; Chang, Shiou-Chi; Eichorst, John Paul; Ouyang, Mingxing; Li, Julie Y.-S.; Chien, Shu; Wang, Yingxiao

    2014-07-01

    Focal adhesions (FAs) are dynamic subcellular structures crucial for cell adhesion, migration and differentiation. It remains an enigma how enzymatic activities in these local complexes regulate their structural remodeling in live cells. Utilizing biosensors based on fluorescence resonance energy transfer (FRET), we developed a correlative FRET imaging microscopy (CFIM) approach to quantitatively analyze the subcellular coordination between the enzymatic Src activation and the structural FA disassembly. CFIM reveals that the Src kinase activity only within the microdomain of lipid rafts at the plasma membrane is coupled with FA dynamics. FA disassembly at cell periphery was linearly dependent on this raft-localized Src activity, although cells displayed heterogeneous levels of response to stimulation. Within lipid rafts, the time delay between Src activation and FA disassembly was 1.2 min in cells seeded on low fibronectin concentration ([FN]) and 4.3 min in cells on high [FN]. CFIM further showed that the level of Src-FA coupling, as well as the time delay, was regulated by cell-matrix interactions, as a tight enzyme-structure coupling occurred in FA populations mediated by integrin αvβ3, but not in those by integrin α5β1. Therefore, different FA subpopulations have distinctive regulation mechanisms between their local kinase activity and structural FA dynamics.

  11. Decipher the dynamic coordination between enzymatic activity and structural modulation at focal adhesions in living cells.

    PubMed

    Lu, Shaoying; Seong, Jihye; Wang, Yi; Chang, Shiou-chi; Eichorst, John Paul; Ouyang, Mingxing; Li, Julie Y-S; Chien, Shu; Wang, Yingxiao

    2014-01-01

    Focal adhesions (FAs) are dynamic subcellular structures crucial for cell adhesion, migration and differentiation. It remains an enigma how enzymatic activities in these local complexes regulate their structural remodeling in live cells. Utilizing biosensors based on fluorescence resonance energy transfer (FRET), we developed a correlative FRET imaging microscopy (CFIM) approach to quantitatively analyze the subcellular coordination between the enzymatic Src activation and the structural FA disassembly. CFIM reveals that the Src kinase activity only within the microdomain of lipid rafts at the plasma membrane is coupled with FA dynamics. FA disassembly at cell periphery was linearly dependent on this raft-localized Src activity, although cells displayed heterogeneous levels of response to stimulation. Within lipid rafts, the time delay between Src activation and FA disassembly was 1.2 min in cells seeded on low fibronectin concentration ([FN]) and 4.3 min in cells on high [FN]. CFIM further showed that the level of Src-FA coupling, as well as the time delay, was regulated by cell-matrix interactions, as a tight enzyme-structure coupling occurred in FA populations mediated by integrin αvβ₃, but not in those by integrin α₅β₁. Therefore, different FA subpopulations have distinctive regulation mechanisms between their local kinase activity and structural FA dynamics.

  12. Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling.

    PubMed

    Krishnamurthy, Srinath; Tulsian, Nikhil Kumar; Chandramohan, Arun; Anand, Ganesh S

    2015-09-15

    The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown. Specifically, the binding and allosteric networks that regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear. In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respectively) were used as a model system to monitor complex formation in the presence and absence of cAMP. Amide hydrogen/deuterium exchange mass spectrometry was used to monitor slow conformational transitions in RD, using disordered regions as conformational probes. Our results reveal that RD regulates its interactions with cAMP and RegA at distinct loci by undergoing slow conformational transitions between two metastable states. In the presence of cAMP, RD and RegA form a stable ternary complex, while in the absence of cAMP they maintain transient interactions. RegA and cAMP each bind at orthogonal sites on RD with resultant contrasting effects on its dynamics through parallel allosteric relays at multiple important loci. RD thus serves as an integrative node in cAMP termination by coordinating multiple allosteric relays and governing the output signal response.

  13. Tracking Active Region NOAA 12192 in Multiple Carrington Rotations

    NASA Astrophysics Data System (ADS)

    Jain, Kiran; Tripathy, Sushant C.; Hill, Frank

    2015-04-01

    Active region NOAA 12192 appeared on the visible solar disk on October 18, 2014 and grew rapidly into the largest such region since 1990. During its entire transit across the Earth facing side of the Sun, it produced a significant number of X- and M-class flares. The combination of front-side and helioseismic far-side images clearly indicated that it lived through several Carrington rotations. In this paper, using Dopplergrams from GONG and HMI, we present a study on mode parameters, viz. oscillation frequencies, amplitude, and sub-surface flows and investigate how these vary with the evolution of active region in multiple rotations. We also present a detailed comparison between NOAA 10486 (the biggest active region in cycle 23) and NOAA 12192, and discuss the similarities/differences between them.

  14. Coordinated integrin activation by actin-dependent force during T-cell migration

    PubMed Central

    Nordenfelt, Pontus; Elliott, Hunter L.; Springer, Timothy A.

    2016-01-01

    For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration. PMID:27721490

  15. Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks

    PubMed Central

    Chanut, Pauline; Britton, Sébastien; Coates, Julia; Jackson, Stephen P.; Calsou, Patrick

    2016-01-01

    Repair of single-ended DNA double-strand breaks (seDSBs) by homologous recombination (HR) requires the generation of a 3′ single-strand DNA overhang by exonuclease activities in a process called DNA resection. However, it is anticipated that the highly abundant DNA end-binding protein Ku sequesters seDSBs and shields them from exonuclease activities. Despite pioneering works in yeast, it is unclear how mammalian cells counteract Ku at seDSBs to allow HR to proceed. Here we show that in human cells, ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on seDSBs. We also provide evidence for a hitherto unsuspected additional mechanism that contributes to prevent Ku accumulation at seDSBs, acting downstream of MRE11 endonuclease activity and in parallel with MRE11 exonuclease activity. Finally, we show that Ku persistence at seDSBs compromises Rad51 focus assembly but not DNA resection. PMID:27641979

  16. Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks.

    PubMed

    Chanut, Pauline; Britton, Sébastien; Coates, Julia; Jackson, Stephen P; Calsou, Patrick

    2016-01-01

    Repair of single-ended DNA double-strand breaks (seDSBs) by homologous recombination (HR) requires the generation of a 3' single-strand DNA overhang by exonuclease activities in a process called DNA resection. However, it is anticipated that the highly abundant DNA end-binding protein Ku sequesters seDSBs and shields them from exonuclease activities. Despite pioneering works in yeast, it is unclear how mammalian cells counteract Ku at seDSBs to allow HR to proceed. Here we show that in human cells, ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on seDSBs. We also provide evidence for a hitherto unsuspected additional mechanism that contributes to prevent Ku accumulation at seDSBs, acting downstream of MRE11 endonuclease activity and in parallel with MRE11 exonuclease activity. Finally, we show that Ku persistence at seDSBs compromises Rad51 focus assembly but not DNA resection. PMID:27641979

  17. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes

    PubMed Central

    Dawe, G. Brent; Musgaard, Maria; Aurousseau, Mark R.P.; Nayeem, Naushaba; Green, Tim; Biggin, Philip C.; Bowie, Derek

    2016-01-01

    Summary Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. PMID:26924438

  18. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes.

    PubMed

    Dawe, G Brent; Musgaard, Maria; Aurousseau, Mark R P; Nayeem, Naushaba; Green, Tim; Biggin, Philip C; Bowie, Derek

    2016-03-16

    Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. PMID:26924438

  19. Pathway connectivity and signaling coordination in the yeast stress-activated signaling network

    PubMed Central

    Chasman, Deborah; Ho, Yi-Hsuan; Berry, David B; Nemec, Corey M; MacGilvray, Matthew E; Hose, James; Merrill, Anna E; Lee, M Violet; Will, Jessica L; Coon, Joshua J; Ansari, Aseem Z; Craven, Mark; Gasch, Audrey P

    2014-01-01

    Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. PMID:25411400

  20. The influence of crossbite on the coordinated electromyographic activity of human masticatory muscles during mastication.

    PubMed

    Ferrario, V F; Sforza, C; Serrao, G

    1999-07-01

    The analysis of the masticatory muscle activity in subjects with altered occlusal relationships could provide useful data of the functional impact of morphological discrepancies. Thirty subjects aged 16-18 years, with a sound, full permanent dentition, bilateral angle class I, and an overjet and overbite between 2 and 5 mm, were examined. The control group (10 male, 10 female) had no crossbite, while the crossbite group (four male, six female) had a posterior unilateral crossbite (five on the left side, five on the right side). The electromyographic activity of the left and right masseter and temporalis anterior muscles was recorded during 15 s of unilateral (left and right) chewing of gum, and expressed as a percentage of the maximum voluntary clench on cotton rolls. For each subject, the masticatory frequency, the confidence ellipse of the simultaneous differential left-right masseter and temporal activity (Lissajous figure), and an index of muscular symmetry, were computed to assess muscular coordination. In the crossbite subjects, the four analysed muscles appeared to contract with altered and asymmetric patterns. A large variability was found, and the confidence ellipses calculated for the chewing tests performed on the crossed sides were not significant, while the confidence ellipses of the uncrossed side chewing were different from the ellipses computed in the normal occlusion group. The altered occlusal relationship influenced the coordination of the masticatory muscles during chewing on both sides. The functional alteration was more apparent when the side with the altered morphology was directly involved, i.e. when chewing was performed on the crossbite side.

  1. A Wolf Pack Algorithm for Active and Reactive Power Coordinated Optimization in Active Distribution Network

    NASA Astrophysics Data System (ADS)

    Zhuang, H. M.; Jiang, X. J.

    2016-08-01

    This paper presents an active and reactive power dynamic optimization model for active distribution network (ADN), whose control variables include the output of distributed generations (DGs), charge or discharge power of energy storage system (ESS) and reactive power from capacitor banks. To solve the high-dimension nonlinear optimization model, a new heuristic swarm intelligent method, namely wolf pack algorithm (WPA) with better global convergence and computational robustness, is adapted so that the network loss minimization can be achieved. In this paper, the IEEE33-bus system is used to show the effectiveness of WPA technique compared with other techniques. Numerical tests on the modified IEEE 33-bus system show that WPA for active and reactive multi-period optimization of ADN is exact and effective.

  2. Effective coordination number: A simple indicator of activation energies for NO dissociation on Rh(100) surfaces

    SciTech Connect

    Ghosh, Prasenjit; Pushpa, Raghani; Gironcoli, Stefano de

    2009-12-15

    We have used density-functional theory to compute the activation energy for the dissociation of NO on two physical and two hypothetical systems: unstrained and strained Rh(100) surfaces and monolayers of Rh atoms on strained and unstrained MgO(100) surfaces. We find that the activation energy, relative to the gas phase, is reduced when a monolayer of Rh is placed on MgO, due both to the chemical nature of the substrate and the strain imposed by the substrate. The former effect is the dominant one, though both effects are of the same order of magnitude. We find that both effects are encapsulated in a simple quantity which we term as the 'effective coordination number'(n{sub e}); the activation energy is found to vary linearly with n{sub e}. We have compared the performance of n{sub e} as a predictor of activation energy of NO dissociation on the above-mentioned Rh surfaces with the two well-established indicators, namely, the position of the d-band center and the coadsorption energy of N and O. We find that for the present systems n{sub e} performs as well as the other two indicators.

  3. Heterogeneity of dynein structure implies coordinated suppression of dynein motor activity in the axoneme.

    PubMed

    Maheshwari, Aditi; Ishikawa, Takashi

    2012-08-01

    Axonemal dyneins provide the driving force for flagellar/ciliary bending. Nucleotide-induced conformational changes of flagellar dynein have been found both in vitro and in situ by electron microscopy, and in situ studies demonstrated the coexistence of at least two conformations in axonemes in the presence of nucleotides (the apo and the nucleotide-bound forms). The distribution of the two forms suggested cooperativity between adjacent dyneins on axonemal microtubule doublets. Although the mechanism of such cooperativity is unknown it might be related to the mechanism of bending. To explore the mechanism by which structural heterogeneity of axonemal dyneins is induced by nucleotides, we used cilia from Tetrahymena thermophila to examine the structure of dyneins in a) the intact axoneme and b) microtubule doublets separated from the axoneme, both with and without additional pure microtubules. We also employed an ATPase assay on these specimens to investigate dynein activity functionally. Dyneins on separated doublets show more activation by nucleotides than those in the intact axoneme, both structurally and in the ATPase assay, and this is especially pronounced when the doublets are coupled with added microtubules, as expected. Paralleling the reduced ATPase activity in the intact axonemes, a lower proportion of these dyneins are in the nucleotide-bound form. This indicates a coordinated suppression of dynein activity in the axoneme, which could be the key for understanding the bending mechanism.

  4. Open Discussion Session: Challenges and Advancements in Coordinated Space Weather Activities

    NASA Astrophysics Data System (ADS)

    Kauristie, Kirsti

    2016-07-01

    Besides addressing the key questions in space weather research the Cospar/ILWS Roadmap presents also recommendations for teaming in the research environment and for collaboration between agencies and communities. Coordinated work of different research groups facilitate our efforts for a holistic view on the entire Sun-Earth system with its complicated feedback processes in different scale sizes. Seamless knowledge transfer from research to operational services is a crucial factor for the success of space weather research field. In this open discussion session we encourage the participants to share their views on most important challenges and advancements in our field, both in science and in collaboration. We also welcome comments on the roadmap recommendations and guidance for similar activities in the future.

  5. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

    PubMed Central

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening

  6. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

    PubMed Central

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening

  7. Coordinated electromyographic activity of the human masseter and temporalis anterior muscles during mastication.

    PubMed

    Ferrario, V F; Sforza, C

    1996-01-01

    The present report aimed at evaluating the within- and between-subject electromyographic coordination between the masseter (M) and temporalis anterior (T) muscles during the performance of a standardized chewing task. Electromyographic activity of M and T muscles was recorded in 60 young healthy adults (30 men, 30 women) during two 15-s unilateral mastications of gum. Left-right differential potentials (delta M = MR-ML, delta T = TR-TL) were computed and the square root of (delta M2 + delta T2) moduli were calculated. The maximum modulus relative to each masticatory cycle was located, and each modulus and differential potential were expressed as a % of the maximum modulus for each subject and chewing trial. For each subject and chewing side, the masticatory frequency was computed, and statistics of the moduli as %s of the maximum were determined by means of bivariate analysis. Within-subject repeatability of the unilateral chewing patterns was good. Mean population values for the modulus position (bivariate analysis), chewing frequency, and maximum modulus of the differential potentials (univariate statistics) were computed. A significant gender difference was found for the masticatory frequency, with larger values in men than in women. Conversely, no gender or side differences were found for the mean values of the maximum modulus or for the mean position of the percentage moduli. The chewing test applied allowed the evaluation of the neuromuscular coordination during the performance of a standardized physiologic activity. In particular, it quantified the within-subject and chewing side repeatability of the muscular pattern.

  8. Coordinated motor activity in simulated spinal networks emerges from simple biologically plausible rules of connectivity.

    PubMed

    Dale, Nicholas

    2003-01-01

    The spinal motor circuits of the Xenopus embryo have been simulated in a 400-neuron network. To explore the consequences of differing patterns of synaptic connectivity within the network for the generation of the motor rhythm, a system of biologically plausible rules was devised to control synapse formation by three parameters. Each neuron had an intrinsic probability of synapse formation (P(soma), specified by a space constant lambda) that was a monotonically decreasing function of its soma location in the rostro-caudal axis of the simulated network. The neurons had rostral and caudal going axons of specified length (L(axon)) associated with a probability of synapse formation (P(axon)). The final probability of synapse formation was the product of P(soma) and P(axon). Realistic coordinated activity only occurred when L(axon) and the probabilities of interconnection were sufficiently high. Increasing the values of the three network parameters reduced the burst duration, cycle period, and rostro-caudal delay and increased the reliability with which the network functioned as measured by the coefficient of variance of these parameters. Whereas both L(axon) and P(axon) had powerful and consistent effects on network output, the effects of lambda on burst duration and rostro-caudal delay were more variable and depended on the values of the other two parameters. This network model can reproduce the rostro-caudal coordination of swimming without using coupled oscillator theory. The changes in network connectivity and resulting changes in activity explored by the model mimic the development of the motor pattern for swimming in the real embryo.

  9. Resource Constrained Planning of Multiple Projects with Separable Activities

    NASA Astrophysics Data System (ADS)

    Fujii, Susumu; Morita, Hiroshi; Kanawa, Takuya

    In this study we consider a resource constrained planning problem of multiple projects with separable activities. This problem provides a plan to process the activities considering a resource availability with time window. We propose a solution algorithm based on the branch and bound method to obtain the optimal solution minimizing the completion time of all projects. We develop three methods for improvement of computational efficiency, that is, to obtain initial solution with minimum slack time rule, to estimate lower bound considering both time and resource constraints and to introduce an equivalence relation for bounding operation. The effectiveness of the proposed methods is demonstrated by numerical examples. Especially as the number of planning projects increases, the average computational time and the number of searched nodes are reduced.

  10. Learning Activity Models for Multiple Agents in a Smart Space

    NASA Astrophysics Data System (ADS)

    Crandall, Aaron; Cook, Diane J.

    With the introduction of more complex intelligent environment systems, the possibilities for customizing system behavior have increased dramatically. Significant headway has been made in tracking individuals through spaces using wireless devices [1, 18, 26] and in recognizing activities within the space based on video data (see chapter by Brubaker et al. and [6, 8, 23]), motion sensor data [9, 25], wearable sensors [13] or other sources of information [14, 15, 22]. However, much of the theory and most of the algorithms are designed to handle one individual in the space at a time. Resident tracking, activity recognition, event prediction, and behavior automation becomes significantly more difficult for multi-agent situations, when there are multiple residents in the environment.

  11. Transcriptional activation by pRB and its coordination with SWI/SNF recruitment.

    PubMed

    Flowers, Stephen; Beck, George R; Moran, Elizabeth

    2010-11-01

    A central question in cancer biology is why most tumor susceptibility genes are linked with only limited types of cancer. Human germ-line mutation of the retinoblastoma susceptibility gene Rb1 is closely linked with just retinoblastoma and osteosarcoma, although the gene is universally expressed. Functional analysis of pRB and its close relatives, p107 and p130, has largely focused on their roles in repression of proliferation across all tissue types, but genetic evidence indicates an active requirement for pRB in osteoblast differentiation that correlates more directly with osteosarcoma susceptibility. Still, potential promoter targets of pRB and its role in normally differentiating osteoblasts remain insufficiently characterized. Here, an early marker of osteoblast differentiation, alkaline phosphatase, is identified as a direct promoter activation target of pRB. One role of pRB on this promoter is to displace the histone lysine demethylase KDM5A, thereby favoring trimethylation of H3K4, a promoter activation mark. A major new aspect of pRB-mediated transcriptional activation revealed in this promoter analysis is its role in recruitment of an activating SWI/SNF chromatin-remodeling complex. SWI/SNF is a critical coordinator of tissue-specific gene expression. In osteoblasts, SWI/SNF complexes containing the BRM ATPase repress osteoblast-specific genes to maintain the precursor state, whereas the alternative ATPase BRG1 distinguishes an activating SWI/SNF complex necessary for RNA polymerase-II recruitment. A switch from BRM to BRG1 on the alkaline phosphatase promoter marks the onset of differentiation and is accomplished in a precise two-step mechanism. Dissociation of BRM-containing SWI/SNF depends on p300, and association of BRG1-containing SWI/SNF depends on pRB.

  12. Activity Participation Intensity Is Associated with Skeletal Development in Pre-Pubertal Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Tsang, William W. N.; Guo, X.; Fong, Shirley S. M.; Mak, Kwok-Kei; Pang, Marco Y. C.

    2012-01-01

    Purpose: This study aimed (1) to compare the skeletal maturity and activity participation pattern between children with and without developmental coordination disorder (DCD); and (2) to determine whether activity participation pattern was associated with the skeletal development among children with DCD. Materials and methods: Thirty-three children…

  13. Mirror neuron activation in children with developmental coordination disorder: A functional MRI study.

    PubMed

    Reynolds, Jess E; Licari, Melissa K; Billington, Jac; Chen, Yihui; Aziz-Zadeh, Lisa; Werner, Julie; Winsor, Anne M; Bynevelt, Michael

    2015-12-01

    The aim of this study was to reveal cortical areas that may contribute to the movement difficulties seen in children with Developmental Coordination Disorder (DCD). Specifically, we hypothesized that there may be a deficit in the mirror neuron system (MNS), a neural system that responds to both performed and observed actions. Using functional MRI, 14 boys with DCD (x=10.08 years ± 1.31, range=7.83-11.58 years) and 12 typically developing controls (x=10.10 years ± 1.15, range=8.33-12.00 years) were scanned observing, executing and imitating a finger sequencing task using their right hand. Cortical activations of mirror neuron regions, including posterior inferior frontal gyrus (IFG), ventral premotor cortex, anterior inferior parietal lobule and superior temporal sulcus were examined. Children with DCD had decreased cortical activation mirror neuron related regions, including the precentral gyrus and IFG, as well as in the posterior cingulate and precuneus complex when observing the sequencing task. Region of interest analysis revealed lower activation in the pars opercularis, a primary MNS region, during imitation in the DCD group compared to controls. These findings provide some preliminary evidence to support a possible MNS dysfunction in children with DCD. PMID:26523778

  14. M2L4 coordination capsules with tunable anticancer activity upon guest encapsulation.

    PubMed

    Ahmedova, Anife; Mihaylova, Rositsa; Momekova, Denitsa; Shestakova, Pavletta; Stoykova, Silviya; Zaharieva, Joana; Yamashina, Masahiro; Momekov, Georgi; Akita, Munetaka; Yoshizawa, Michito

    2016-08-16

    Metallosupramolecular cages and capsules have gained increasing popularity as both molecular containers and anticancer agents. For successful combination of these properties a thorough analysis of the effect of guest encapsulation on the host's cytotoxic properties is highly required. Here we report on the cytotoxicity modulation of Pt(ii) and Pd(ii)-linked M2L4 coordination capsules upon encapsulation of guest molecules such as pyrene and caffeine. The anticancer activity of the capsules against various human cancer cells (HT-29, T-24, HL-60 and its resistant counterparts HL-60/Dox and HL-60/CDDP) significantly altered upon the guest encapsulation. The encapsulation of pyrene molecules causes a decrease in the cytotoxicity of the Pt(ii) capsule, which is stronger than that of the Pd(ii) capsule. The cytotoxicities of the caffeine containing capsules are lower than that of the empty capsules (except for HL-60), but still superior to cisplatin under the same conditions. The observed trends in the anticancer activity of the capsules and their host-guest complexes correlate with their different stabilities toward glutathione, estimated by NMR-based kinetic experiments. Mechanistic insights into the observed cytotoxicities are obtained by fluorescence microscopy imaging of tumor cells treated with the capsules and their pyrene complexes. The data suggest the glutathione-triggered disassembly of the capsular structures as a potential activation pathway for their cytotoxicities. PMID:27488015

  15. Mcm10 coordinates the timely assembly and activation of the replication fork helicase.

    PubMed

    Perez-Arnaiz, Patricia; Bruck, Irina; Kaplan, Daniel L

    2016-01-01

    Mcm10 is an essential replication factor that is required for DNA replication in eukaryotes. Two key steps in the initiation of DNA replication are the assembly and activation of Cdc45-Mcm2-7-GINS (CMG) replicative helicase. However, it is not known what coordinates helicase assembly with helicase activation. We show in this manuscript, using purified proteins from budding yeast, that Mcm10 directly interacts with the Mcm2-7 complex and Cdc45. In fact, Mcm10 recruits Cdc45 to Mcm2-7 complex in vitro. To study the role of Mcm10 in more detail in vivo we used an auxin inducible degron in which Mcm10 is degraded upon addition of auxin. We show in this manuscript that Mcm10 is required for the timely recruitment of Cdc45 and GINS recruitment to the Mcm2-7 complex in vivo during early S phase. We also found that Mcm10 stimulates Mcm2 phosphorylation by DDK in vivo and in vitro. These findings indicate that Mcm10 plays a critical role in coupling replicative helicase assembly with helicase activation. Mcm10 is first involved in the recruitment of Cdc45 to the Mcm2-7 complex. After Cdc45-Mcm2-7 complex assembly, Mcm10 promotes origin melting by stimulating DDK phosphorylation of Mcm2, which thereby leads to GINS attachment to Mcm2-7.

  16. Tax-interacting protein 1 coordinates the spatiotemporal activation of Rho GTPases and regulates the infiltrative growth of human glioblastoma

    PubMed Central

    Wang, Hailun; Han, Miaojun; Whetsell, William; Wang, Jialiang; Rich, Jeremy; Hallahan, Dennis; Han, Zhaozhong

    2014-01-01

    PDZ domains represent one group of the major structural units that mediate protein interactions in intercellular contact, signal transduction and assembly of biological machineries. TIP-1 protein is composed of a single PDZ domain that distinguishes TIP-1 from other PDZ domain proteins that more often contain multiple protein domains and function as scaffolds for protein complex assembly. However, the biological functions of TIP-1, especially in cell transformation and tumor progression, are still controversial as observed in a variety of cell types. In this study, we have identified ARHGEF7, a guanine nucleotide exchange factor (GEF) for Rho GTPases, as one novel TIP-1 interacting protein in human glioblastoma cells. We found that the presence of TIP-1 protein is essential to the intracellular redistribution of ARHGEF7 and rhotekin, one Rho effector, and the spatiotemporally coordinated activation of Rho GTPases (RhoA, Cdc42 and Rac1) in migrating glioblastoma cells. TIP-1 knockdown resulted in both aberrant localization of ARHGEF7 and rhotekin, as well as abnormal activation of Rho GTPases that was accompanied with impaired motility of glioblastoma cells. Furthermore, TIP-1 knockdown suppressed tumor cell dispersal in orthotopic glioblastoma murine models. We also observed high levels of TIP-1 expression in human glioblastoma specimens, and the elevated TIP-1 levels are associated with advanced staging and poor prognosis in glioma patients. Although more studies are needed to further dissect the mechanism(s) by which TIP-1 modulates the intracellular redistribution and activation of Rho GTPases, this study suggests that TIP-1 holds potential as both a prognostic biomarker and a therapeutic target of malignant gliomas. PMID:23563176

  17. Coronal Magnetography of Solar Active Regions Using Coordinated SOHO/CDS and VLA Observations

    NASA Technical Reports Server (NTRS)

    Brosius, Jeffrey W.

    1999-01-01

    The purpose of this project is to apply the coronal magnetographic technique to SOHO (Solar Heliospheric Observatory) /CDS (Coronal Diagnostic Spectrometer) EUV (Extreme Ultraviolet Radiation) and coordinated VLA microwave observations of solar active regions to derive the strength and structure of the coronal magnetic field. A CDS observing plan was developed for obtaining spectra needed to derive active region differential emission measures (DEMs) required for coronal magnetography. VLA observations were proposed and obtained. SOHO JOP 100 was developed, tested, approved, and implemented to obtain coordinated CDS (Coronal Diagnostic Spectrometer)/EIT (Ultraviolet Imaging Telescope)/ VLA (Very Large Array)/ TRACE (Transition Region and Coronal Explorer)/ SXT (Solar X Ray Telescope) observations of active regions on April 12, May 9, May 13, and May 23. Analysis of all four data sets began, with heaviest concentration on COS data. It is found that 200-pixel (14 A in NIS1) wavelength windows are appropriate for extracting broadened Gaussian line profile fit parameters for lines including Fe XIV at 334.2, Fe XVI at 335.4, Fe XVI at 360.8, and Mg IX at 368.1 over the 4 arcmin by 4 arcmin CDS field of view. Extensive efforts were focused on learning and applying were focused on learning and applying CDS software, and including it in new IDL procedures to carry out calculations relating to coronal magnetography. An important step is to extract Gaussian profile fits to all the lines needed to derive the DEM in each spatial pixel of any given active region. The standard CDS absolute intensity calibration software was applied to derived intensity images, revealing that ratios between density-insensitive lines like Fe XVI 360.8/335.4 yield good agreement with theory. However, the resulting absolute intensities of those lines are very high, indicating that revisions to the CDS absolute intensity calibrations remain to be included in the CDS software, an essential step to

  18. Laterality of movement-related activity reflects transformation of coordinates in ventral premotor cortex and primary motor cortex of monkeys.

    PubMed

    Kurata, Kiyoshi

    2007-10-01

    The ventral premotor cortex (PMv) and the primary motor cortex (MI) of monkeys participate in various sensorimotor integrations, such as the transformation of coordinates from visual to motor space, because the areas contain movement-related neuronal activity reflecting either visual or motor space. In addition to relationship to visual and motor space, laterality of the activity could indicate stages in the visuomotor transformation. Thus we examined laterality and relationship to visual and motor space of movement-related neuronal activity in the PMv and MI of monkeys performing a fast-reaching task with the left or right arm, toward targets with visual and motor coordinates that had been dissociated by shift prisms. We determined laterality of each activity quantitatively and classified it into four types: activity that consistently depended on target locations in either head-centered visual coordinates (V-type) or motor coordinates (M-type) and those that had either differential or nondifferential activity for both coordinates (B- and N-types). A majority of M-type neurons in the areas had preferences for reaching movements with the arm contralateral to the hemisphere where neuronal activity was recorded. In contrast, most of the V-type neurons were recorded in the PMv and exhibited less laterality than the M-type. The B- and N-types were recorded in the PMv and MI and exhibited intermediate properties between the V- and M-types when laterality and correlations to visual and motor space of them were jointly examined. These results suggest that the cortical motor areas contribute to the transformation of coordinates to generate final motor commands.

  19. Brain Activation of Identity Switching in Multiple Identity Tracking Task.

    PubMed

    Lyu, Chuang; Hu, Siyuan; Wei, Liuqing; Zhang, Xuemin; Talhelm, Thomas

    2015-01-01

    When different objects switch identities in the multiple identity tracking (MIT) task, viewers need to rebind objects' identity and location, which requires attention. This rebinding helps people identify the regions targets are in (where they need to focus their attention) and inhibit unimportant regions (where distractors are). This study investigated the processing of attentional tracking after identity switching in an adapted MIT task. This experiment used three identity-switching conditions: a target-switching condition (where the target objects switched identities), a distractor-switching condition (where the distractor objects switched identities), and a no-switching condition. Compared to the distractor-switching condition, the target-switching condition elicited greater activation in the frontal eye fields (FEF), intraparietal sulcus (IPS), and visual cortex. Compared to the no-switching condition, the target-switching condition elicited greater activation in the FEF, inferior frontal gyrus (pars orbitalis) (IFG-Orb), IPS, visual cortex, middle temporal lobule, and anterior cingulate cortex. Finally, the distractor-switching condition showed greater activation in the IFG-Orb compared to the no-switching condition. These results suggest that, in the target-switching condition, the FEF and IPS (the dorsal attention network) might be involved in goal-driven attention to targets during attentional tracking. In addition, in the distractor-switching condition, the activation of the IFG-Orb may indicate salient change that pulls attention away automatically.

  20. Eurocan plus report: feasibility study for coordination of national cancer research activities.

    PubMed

    2008-01-01

    The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe-wide consultation ever conducted in the field of cancer research.Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.It is essential to include the patients' voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes

  1. Posttranslational regulation of coordinated enzyme activities in the Pup-proteasome system

    PubMed Central

    Elharar, Yifat; Roth, Ziv; Hecht, Nir; Rotkopf, Ron; Khalaila, Isam; Gur, Eyal

    2016-01-01

    The proper functioning of any biological system depends on the coordinated activity of its components. Regulation at the genetic level is, in many cases, effective in determining the cellular levels of system components. However, in cases where regulation at the genetic level is insufficient for attaining harmonic system function, posttranslational regulatory mechanisms are often used. Here, we uncover posttranslational regulatory mechanisms in the prokaryotic ubiquitin-like protein (Pup)-proteasome system (PPS), the bacterial equivalent of the eukaryotic ubiquitin-proteasome system. Pup, a ubiquitin analog, is conjugated to proteins through the activities of two enzymes, Dop (deamidase of Pup) and PafA (proteasome accessory factor A), the Pup ligase. As Dop also catalyzes depupylation, it was unclear how PPS function could be maintained without Dop and PafA canceling the activity of the other, and how the two activities of Dop are balanced. We report that tight Pup binding and the limited degree of Dop interaction with high-molecular-weight pupylated proteins results in preferred Pup deamidation over protein depupylation by this enzyme. Under starvation conditions, when accelerated protein pupylation is required, this bias is intensified by depletion of free Dop molecules, thereby minimizing the chance of depupylation. We also find that, in contrast to Dop, PafA presents a distinct preference for high-molecular-weight protein substrates. As such, PafA and Dop act in concert, rather than canceling each other's activity, to generate a high-molecular-weight pupylome. This bias in pupylome molecular weight distribution is consistent with the proposed nutritional role of the PPS under starvation conditions. PMID:26951665

  2. Enzyme Design From the Bottom Up: An Active Nickel Electrocatalyst with a Structured Peptide Outer Coordination Sphere

    SciTech Connect

    Reback, Matthew L.; Buchko, Garry W.; Kier, Brandon L.; Ginovska-Pangovska, Bojana; Xiong, Yijia; Lense, Sheri; Hou, Jianbo; Roberts, John A.; Sorensen, Christina M.; Raugei, Simone; Squier, Thomas C.; Shaw, Wendy J.

    2014-02-03

    Functional, peptide-containing metal complexes with a well-defined peptide structure have the potential to enhance molecular catalysts via an enzyme-like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide-based metal complex built upon the well characterized hydrogen production catalyst, Ni(PPh2NPh)2. The incorporated peptide maintains its B-hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide-based metal complex (~100,000 s-1) is fully retained. The combination of an active molecular catalyst with a structured peptide outer coordination sphere provides a scaffold that permits the incorporation of features of an enzyme-like outer-coordination sphere necessary to create molecular electrocatalysts with en-hanced functionality.

  3. Photodynamic activity and binding of sulfonated metallophthalocyanines to phospholipid membranes: contribution of metal-phosphate coordination.

    PubMed

    Pashkovskaya, Alina A; Sokolenko, Elena A; Sokolov, Valeri S; Kotova, Elena A; Antonenko, Yuri N

    2007-10-01

    Photosensitized efficacy of tetrasulfonated phthalocyanines of zinc, aluminum and nickel (ZnPcS(4), AlPcS(4) and NiPcS(4), respectively) as studied by gramicidin channel (gA) photoinactivation was compared with adsorption of the dyes on the surface of a bilayer lipid membrane as measured by the inner field compensation method. The adsorption of the negatively charged phthalocyanines on diphytanoylphosphatidylcholine (DPhPC) membranes led to formation of a negative boundary potential difference between the membrane/water interfaces. Good correlation was shown between the photodynamic activity and the membrane binding of the three metallophthalocyanines. ZnPcS(4) appeared to be the most potent of these photosensitizers, while NiPcS(4) was completely ineffective. All of these phthalocyanines displayed no binding and negligible gA photoinactivation with membranes formed of glycerol monooleate (GMO), whereas Rose Bengal exhibited significant binding and photodynamic efficacy with GMO membranes. Gramicidin photoinactivation in the presence of AlPcS(4), being insensitive to the ionic strength of the bathing solution, was inhibited by fluoride and attenuated by phosphate ions. A blue shift of the fluorescence peak position of ZnPcS(4) dissolved in ethanol was elicited by phosphate, similarly to fluoride, which was indicative of the coordination interaction of these ions with the central metal atom of the phthalocyanine macrocycle. This interaction was enhanced in the medium modeling the water-membrane interface. The results obtained imply that binding of tetrasulfonated metallophthalocyanines to phospholipid membranes is determined primarily by metal-phosphate coordination.

  4. Optimal wide-area monitoring and nonlinear adaptive coordinating neurocontrol of a power system with wind power integration and multiple FACTS devices.

    PubMed

    Qiao, Wei; Venayagamoorthy, Ganesh K; Harley, Ronald G

    2008-01-01

    Wide-area coordinating control is becoming an important issue and a challenging problem in the power industry. This paper proposes a novel optimal wide-area coordinating neurocontrol (WACNC), based on wide-area measurements, for a power system with power system stabilizers, a large wind farm and multiple flexible ac transmission system (FACTS) devices. An optimal wide-area monitor (OWAM), which is a radial basis function neural network (RBFNN), is designed to identify the input-output dynamics of the nonlinear power system. Its parameters are optimized through particle swarm optimization (PSO). Based on the OWAM, the WACNC is then designed by using the dual heuristic programming (DHP) method and RBFNNs, while considering the effect of signal transmission delays. The WACNC operates at a global level to coordinate the actions of local power system controllers. Each local controller communicates with the WACNC, receives remote control signals from the WACNC to enhance its dynamic performance and therefore helps improve system-wide dynamic and transient performance. The proposed control is verified by simulation studies on a multimachine power system.

  5. Active Joint Mechanism Driven by Multiple Actuators Made of Flexible Bags: A Proposal of Dual Structural Actuator

    PubMed Central

    Inou, Norio

    2013-01-01

    An actuator is required to change its speed and force depending on the situation. Using multiple actuators for one driving axis is one of the possible solutions; however, there is an associated problem of output power matching. This study proposes a new active joint mechanism using multiple actuators. Because the actuator is made of a flexible bag, it does not interfere with other actuators when it is depressurized. The proposed joint achieved coordinated motion of multiple actuators. This report also discusses a new actuator which has dual cylindrical structure. The cylinders are composed of flexible bags with different diameters. The joint torque is estimated based on the following factors: empirical formula for the flexible actuator torque, geometric relationship between the joint and the actuator, and the principle of virtual work. The prototype joint mechanism achieves coordinated motion of multiple actuators for one axis. With this motion, small inner actuator contributes high speed motion, whereas large outer actuator generates high torque. The performance of the prototype joint is examined by speed and torque measurements. The joint showed about 30% efficiency at 2.0 Nm load torque under 0.15 MPa air input. PMID:24385868

  6. Coordination of bat sonar activity and flight for the exploration of three-dimensional objects.

    PubMed

    Genzel, Daria; Geberl, Cornelia; Dera, Thomas; Wiegrebe, Lutz

    2012-07-01

    The unique combination of flight and echolocation has opened the nocturnal air space as a rich ecological niche for bats. By analysing echoes of their sonar emissions, bats discriminate and recognize three-dimensional (3-D) objects. However, in contrast to vision, the 3-D information that can be gained by ensonifying an object from only one observation angle is sparse. To date, it is unclear how bats synchronize echolocation and flight activity to explore the 3-D shape of ensonified objects. We have devised an experimental design that allows creating 3-D virtual echo-acoustic objects by generating in real-time echoes from the bat's emissions that depend on the bat's position relative to the virtual object. Bats were trained to evaluate these 3-D virtual objects differing in their azimuthal variation of either echo amplitude or spectral composition. The data show that through a very effective coordination of sonar and flight activity, bats analyse an azimuthal variation of echo amplitude with a resolution of approximately 16 dB and a variation of echo centre frequency of approximately 19%. Control experiments show that the bats can detect not only these variations but also perturbations in the spatial arrangement of these variations. The current experimental paradigm shows that echolocating bats assemble echo-acoustic object information - acquired sequentially in flight - to reconstruct the 3-D shape of the ensonified object. Unlike previous approaches, the recruitment of virtual objects allows for a direct quantification of this reconstruction success in a highly controlled experimental approach.

  7. [Aluminum coordination and active sites on aluminas, Y-zeolites and pillared layered silicates]. Progress report

    SciTech Connect

    Fripiat, J.J.

    1994-02-01

    This report is organized in four sections. In the first the authors will outline structural features which are common to all fine grained alumina, as well as to non-framework alumina in zeolites. This section will be followed by a study of the surface vs. bulk coordination of aluminum. The third section will deal with measurement of the number of acid sites and the scaling of their strength. The fourth and last section will describe three model reactions: the isomerization of 1-butene and of 2 cis-butene; the isomerization and disproportionation of oxtho-xylene; and the transformation of trichloroethane into vinyl chloride followed by the polymerization of the vinyl chloride. The relationship between chemical activity and selectivity and what is known of the local structure of the active catalytic sites will be underlined. Other kinds of zeolites besides Y zeolite have been studied. Instead of the aluminum pillared silicates they found it more interesting to study the substitution of silicon by aluminum in a layered structure containing a permanent porosity (aluminated sepiolite).

  8. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin.

    PubMed

    Dölen, Gül; Darvishzadeh, Ayeh; Huang, Kee Wui; Malenka, Robert C

    2013-09-12

    Social behaviours in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviours, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin acts as a social reinforcement signal within the nucleus accumbens core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the nucleus accumbens receives oxytocin-receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-hydroxytryptamine; 5-HT) innervation to the nucleus accumbens, abolishes the reinforcing properties of social interaction. Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-HT1B receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of oxytocin and 5-HT in the nucleus accumbens, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism. PMID:24025838

  9. Spectroscopic properties and the catalytic activity of new organo-lead supramolecular coordination polymer containing quinoxaline

    NASA Astrophysics Data System (ADS)

    Etaiw, Safaa El-din H.; Abdou, Safaa N.

    2015-01-01

    The 3D-supramolecular coordination polymer (SCP) 3∞[ Cu2(CN)3(Me3Pb)(qox)], 1, as the first example of the CuCN SCP containing the (Me3Pb) fragment, was explored to investigate its catalytic and photo-catalytic activities. The structure of 1 contains two chemically identical but crystallographically different [Cu2(CN)3ṡMe3Pbṡqox]2 units with four Cu(I) sites assuming distorted TP-3 geometry. Two non-linear chains of equal abundance are formed producing corrugated parallel chains which are connected laterally by quinoxaline creating 2D-layers which are arranged parallel in an (AB⋯AB⋯AB)n fashion forming 3D-network. IR, mass, electronic absorption and fluorescence spectra are also investigated. The SCP 1 is diamagnetic and exhibits good catalytic and photo-catalytic activities for the degradation of methylene blue (MB). The reaction is first order with respect to MB dye. The irradiation of the reaction with UV-light enhanced the rate of MB mineralization. The efficiency of recycled the 1 and the mechanism of degradation of MB dye were investigated.

  10. Spectroscopic properties and the catalytic activity of new organo-lead supramolecular coordination polymer containing quinoxaline.

    PubMed

    Etaiw, Safaa El-din H; Abdou, Safaa N

    2015-01-25

    The 3D-supramolecular coordination polymer (SCP) (3)∞[ Cu2(CN)3(Me3Pb)(qox)], 1, as the first example of the CuCN SCP containing the (Me3Pb) fragment, was explored to investigate its catalytic and photo-catalytic activities. The structure of 1 contains two chemically identical but crystallographically different [Cu2(CN)3⋅Me3Pb⋅qox]2 units with four Cu(I) sites assuming distorted TP-3 geometry. Two non-linear chains of equal abundance are formed producing corrugated parallel chains which are connected laterally by quinoxaline creating 2D-layers which are arranged parallel in an (AB⋯AB⋯AB)n fashion forming 3D-network. IR, mass, electronic absorption and fluorescence spectra are also investigated. The SCP 1 is diamagnetic and exhibits good catalytic and photo-catalytic activities for the degradation of methylene blue (MB). The reaction is first order with respect to MB dye. The irradiation of the reaction with UV-light enhanced the rate of MB mineralization. The efficiency of recycled the 1 and the mechanism of degradation of MB dye were investigated.

  11. Spectroscopic properties and the catalytic activity of new organo-lead supramolecular coordination polymer containing quinoxaline.

    PubMed

    Etaiw, Safaa El-din H; Abdou, Safaa N

    2015-01-25

    The 3D-supramolecular coordination polymer (SCP) (3)∞[ Cu2(CN)3(Me3Pb)(qox)], 1, as the first example of the CuCN SCP containing the (Me3Pb) fragment, was explored to investigate its catalytic and photo-catalytic activities. The structure of 1 contains two chemically identical but crystallographically different [Cu2(CN)3⋅Me3Pb⋅qox]2 units with four Cu(I) sites assuming distorted TP-3 geometry. Two non-linear chains of equal abundance are formed producing corrugated parallel chains which are connected laterally by quinoxaline creating 2D-layers which are arranged parallel in an (AB⋯AB⋯AB)n fashion forming 3D-network. IR, mass, electronic absorption and fluorescence spectra are also investigated. The SCP 1 is diamagnetic and exhibits good catalytic and photo-catalytic activities for the degradation of methylene blue (MB). The reaction is first order with respect to MB dye. The irradiation of the reaction with UV-light enhanced the rate of MB mineralization. The efficiency of recycled the 1 and the mechanism of degradation of MB dye were investigated. PMID:25124847

  12. Small molecule regulation of self-association and catalytic activity in a supramolecular coordination complex.

    PubMed

    McGuirk, C Michael; Stern, Charlotte L; Mirkin, Chad A

    2014-03-26

    Herein, we report the synthesis and characterization of the first weak-link approach (WLA) supramolecular construct that employs the small molecule regulation of intermolecular hydrogen bonding interactions for the in situ control of catalytic activity. A biaryl urea group, prone to self-aggregation, was functionalized with a phosphinoalkyl thioether (P,S) hemilabile moiety and incorporated into a homoligated Pt(II) tweezer WLA complex. This urea-containing construct, which has been characterized by a single crystal X-ray diffraction study, can be switched in situ from a rigid fully closed state to a flexible semiopen state via Cl(-) induced changes in the coordination mode at the Pt(II) structural node. FT-IR and (1)H NMR spectroscopy studies were used to demonstrate that while extensive urea self-association persists in the flexible semiopen complex, these interactions are deterred in the rigid, fully closed complex because of geometric and steric restraints. Consequently, the urea moieties in the fully closed complex are able to catalyze a Diels-Alder reaction between cyclopentadiene and methyl vinyl ketone to generate 2-acetyl-5-norbornene. The free urea ligand and the semiopen complex show no such activity. The successful incorporation and regulation of a hydrogen bond donating catalyst in a WLA construct open the doors to a vast and rapidly growing catalogue of allosteric catalysts for applications in the detection and amplification of organic analytes.

  13. Activation of endogenous neural stem cells for multiple sclerosis therapy.

    PubMed

    Michailidou, Iliana; de Vries, Helga E; Hol, Elly M; van Strien, Miriam E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

  14. Automated discovery of active motifs in multiple RNA secondary structures

    SciTech Connect

    Wang, J.T.L.; Chang, Chia-Yo; Shapiro, B.A.

    1996-12-31

    In this paper we present a method for discovering approximately common motifs (also known as active motifs) in multiple RNA secondary structures. The secondary structures can be represented as ordered trees (i.e., the order among siblings matters). Motifs in these trees are connected subgraphs that can differ in both substitutions and deletions/insertions. The proposed method consists of two steps: (1) find candidate motifs in a small sample of the secondary structures; (2) search all of the secondary structures to determine how frequently these motifs occur (within the allowed approximation) in the secondary structures. To reduce the running time, we develop two optimization heuristics based on sampling and pattern matching techniques. Experimental results obtained by running these algorithms on both generated data and RNA secondary structures show the good performance of the algorithms. To demonstrate the utility of our algorithms, we discuss their applications to conducting the phylogenetic study of RNA sequences obtained from GenBank.

  15. Activation of endogenous neural stem cells for multiple sclerosis therapy

    PubMed Central

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  16. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  17. Oscillations and multiple steady states in active membrane transport models.

    PubMed

    Vieira, F M; Bisch, P M

    1994-01-01

    The dynamic behavior of some non-linear extensions of the six-state alternating access model for active membrane transport is investigated. We use stoichio-metric network analysis to study the stability of steady states. The bifurcation analysis has been done through standard numerical methods. For the usual six-state model we have proved that there is only one steady state, which is globally asymptotically stable. When we added an autocatalytic step we found self-oscillations. For the competition between a monomer cycle and a dimer cycle, with steps of dimer formation, we have also found self-oscillations. We have also studied models involving the formation of a complex with other molecules. The addition of two steps for formation of a complex of the monomer with another molecule does not alter either the number or the stability of steady states of the basic six-state model. The model which combines the formation of a complex with an autocatalytic step shows both self-oscillations and multiple steady states. The results lead us to conclude that oscillations could be produced by active membrane transport systems if the transport cycle contains a sufficiently large number of steps (six in the present case) and is coupled to at least one autocatalytic reaction,. Oscillations are also predicted when the monomer cycle is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a simplification of the model involving competition between monomer and dimer cycles, which seems to be a more realistic description of biological systems. A self-regulation mechanism of the pumps, related to the multiple stationary states, is expected only for a combined effect of autocatalysis and formation of complexes with other molecules. Within the six-state model this model also leads to oscillation.

  18. Active Hydrogenation Catalyst with a Structured, Peptide-Based Outer-Coordination Sphere

    SciTech Connect

    Jain, Avijita; Buchko, Garry W.; Reback, Matthew L.; O'Hagan, Molly J.; Ginovska-Pangovska, Bojana; Linehan, John C.; Shaw, Wendy J.

    2012-10-05

    The synthesis, catalytic activity, and structural features of a rhodium-based hydrogenation catalyst containing a phosphine ligand coupled to a 14-residue peptide are reported. Both CD and NMR spectroscopy show that the peptide adopts a helical structure in 1:1:1 TFE/MeCN/H2O that is maintained when the peptide is attached to the ligand and when the ligand is attached to the metal complex. The metal complex hydrogenates aqueous solutions of 3-butenol to 1-butanol at 360 ± 50 turnovers/Rh/h at 294 K. This peptide- based catalyst represents a starting point for developing and characterizing a peptide-based outer-coordination sphere that can be used to introduce enzyme-like features into molecular catalysts. This work was funded by the US DOE Basic Energy Sciences, Chemical Sciences, Geoscience and Biosciences Division (AJ, JCL and WJS), the Office of Science Early Career Research Program through the Office of Basic Energy Sciences (GWB, MLR and WJS). Part of the research was conducted at the W.R. Wiley Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by U.S. Department of Energy’s Office of Biolog-ical and Environmental Research (BER) program located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the U.S. Department of Energy.

  19. Increased microglial catalase activity in multiple sclerosis grey matter.

    PubMed

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  20. Mechanisms for multiple activity modes of VTA dopamine neurons

    PubMed Central

    Oster, Andrew; Faure, Philippe; Gutkin, Boris S.

    2015-01-01

    Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta (SNc) DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition. PMID:26283955

  1. BLADE-ON-PETIOLE1 coordinates organ determinacy and axial polarity in Arabidopsis by directly activating ASYMMETRIC LEAVES2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Continuous organ formation is a hallmark of plant development that requires organ-specific gene activity to establish determinacy and axial patterning, yet the molecular mechanisms that coordinate these events remain poorly understood. Here, we show that the organ-specific BTB-POZ domain proteins BL...

  2. The Risk of Reduced Physical Activity in Children with Probable Developmental Coordination Disorder: A Prospective Longitudinal Study

    ERIC Educational Resources Information Center

    Green, Dido; Lingam, Raghu; Mattocks, Calum; Riddoch, Chris; Ness, Andy; Emond, Alan

    2011-01-01

    The aim of the current study was to test the hypothesis that children with probable Developmental Coordination Disorder have an increased risk of reduced moderate to vigorous physical activity (MVPA), using data from a large population based study. Prospectively collected data from 4331 children (boys = 2065, girls = 2266) who had completed motor…

  3. Heterogeneity in the Histidine-brace Copper Coordination Sphere in Auxiliary Activity Family 10 (AA10) Lytic Polysaccharide Monooxygenases.

    PubMed

    Chaplin, Amanda K; Wilson, Michael T; Hough, Michael A; Svistunenko, Dimitri A; Hemsworth, Glyn R; Walton, Paul H; Vijgenboom, Erik; Worrall, Jonathan A R

    2016-06-10

    Copper-dependent lytic polysaccharide monooxygenases (LPMOs) are enzymes that oxidatively deconstruct polysaccharides. The active site copper in LPMOs is coordinated by a histidine-brace. This utilizes the amino group and side chain of the N-terminal His residue with the side chain of a second His residue to create a T-shaped arrangement of nitrogen ligands. We report a structural, kinetic, and thermodynamic appraisal of copper binding to the histidine-brace in an auxiliary activity family 10 (AA10) LPMO from Streptomyces lividans (SliLPMO10E). Unexpectedly, we discovered the existence of two apo-SliLPMO10E species in solution that can each bind copper at a single site with distinct kinetic and thermodynamic (exothermic and endothermic) properties. The experimental EPR spectrum of copper-bound SliLPMO10E requires the simulation of two different line shapes, implying two different copper-bound species, indicative of three and two nitrogen ligands coordinating the copper. Amino group coordination was probed through the creation of an N-terminal extension variant (SliLPMO10E-Ext). The kinetics and thermodynamics of copper binding to SliLPMO10E-Ext are in accord with copper binding to one of the apo-forms in the wild-type protein, suggesting that amino group coordination is absent in the two-nitrogen coordinate form of SliLPMO10E. Copper binding to SliLPMO10B was also investigated, and again it revealed the presence of two apo-forms with kinetics and stoichiometry of copper binding identical to that of SliLPMO10E. Our findings highlight that heterogeneity exists in the active site copper coordination sphere of LPMOs that may have implications for the mechanism of loading copper in the cell. PMID:27129229

  4. Coordination chemistry and biological activity of 5'-OH modified quinoline-B12 derivatives.

    PubMed

    Zelenka, Karel; Brandl, Helmut; Spingler, Bernhard; Zelder, Felix

    2011-10-14

    The consequences of structural modifications at the 5'-OH ribofuranotide moiety of quinoline modified B12 derivatives are discussed in regard of the coordination chemistry, the electrochemical properties and the biological behaviour of the compound.

  5. Porcine MHC classical class I genes are coordinately expressed in superantigen-activated mononuclear cells.

    PubMed

    Kametani, Yoshie; Ohshima, Shino; Kita, Yuki F; Shimada, Shin; Kamiguchi, Hiroshi; Shiina, Takashi; Inoko, Hidetoshi; Kulski, Jerzy K; Ando, Asako

    2012-08-15

    The expression of the major histocompatibility complex (MHC) classical class I genes is important for the adaptive immune response to target virus-infected cells and cancer cells. The up-regulation of the MHC is achieved by hormonal/cytokine signals including IFN-γ-inducible elements. The swine leukocyte antigen (SLA), the MHC class I region of pigs, consists of the duplicated classical class I genes, SLA-1, SLA-2 and SLA-3, but the molecular mechanisms involved in their up-regulation after T cell stimulation have not been fully elucidated. In order to better understand some of the putative regulatory mechanisms of SLA class I gene expression in activated T cells, we examined the coordinated expression of the SLA classical class I, IFN-γ and interferon regulatory factor-1 (IRF-1) genes in the peripheral blood mononuclear cells (PBMCs) of SLA homozygous Clawn miniature swine stimulated for 72 h with either IFN-γ or an enterotoxin produced by Staphylococcus aureus. This enterotoxin, toxic shock syndrome-1 (TSST-1), is known to act as a superantigen (sAG) to activate the T cells in various vertebrate species. We showed by using mAbs and flow cytometry that the CD4(+)CD25(+) cell number of swine PBMCs was also increased by TSST-1 and to a lesser degree by IFN-γ. Time course analyses of the expression of the IFN-γ, IRF-1 and the three classical class I genes, SLA-1, SLA-2, and SLA-3, in PBMCs by quantitative real-time PCR revealed a transitory response to TSST-1 or IFN-γ stimulation. The IFN-γ mRNA levels in the PBMCs were continuously up-regulated over the first 48 h by TSST-1 or IFN-γ. In contrast, SLA class I expression moderately increased at 24h and then decreased to a baseline level or less at 72 h of IFN-γ or TSST-1 stimulation. The three classical SLA class I genes showed similar expression kinetics, although SLA-3 mRNA level was consistently lower than those of SLA-1 and -2. The expression of IRF-1, a modulator of SLA expression, showed similar

  6. Coordinated learning of grid cell and place cell spatial and temporal properties: multiple scales, attention and oscillations.

    PubMed

    Grossberg, Stephen; Pilly, Praveen K

    2014-02-01

    A neural model proposes how entorhinal grid cells and hippocampal place cells may develop as spatial categories in a hierarchy of self-organizing maps (SOMs). The model responds to realistic rat navigational trajectories by learning both grid cells with hexagonal grid firing fields of multiple spatial scales, and place cells with one or more firing fields, that match neurophysiological data about their development in juvenile rats. Both grid and place cells can develop by detecting, learning and remembering the most frequent and energetic co-occurrences of their inputs. The model's parsimonious properties include: similar ring attractor mechanisms process linear and angular path integration inputs that drive map learning; the same SOM mechanisms can learn grid cell and place cell receptive fields; and the learning of the dorsoventral organization of multiple spatial scale modules through medial entorhinal cortex to hippocampus (HC) may use mechanisms homologous to those for temporal learning through lateral entorhinal cortex to HC ('neural relativity'). The model clarifies how top-down HC-to-entorhinal attentional mechanisms may stabilize map learning, simulates how hippocampal inactivation may disrupt grid cells, and explains data about theta, beta and gamma oscillations. The article also compares the three main types of grid cell models in the light of recent data. PMID:24366136

  7. Coordinated learning of grid cell and place cell spatial and temporal properties: multiple scales, attention and oscillations.

    PubMed

    Grossberg, Stephen; Pilly, Praveen K

    2014-02-01

    A neural model proposes how entorhinal grid cells and hippocampal place cells may develop as spatial categories in a hierarchy of self-organizing maps (SOMs). The model responds to realistic rat navigational trajectories by learning both grid cells with hexagonal grid firing fields of multiple spatial scales, and place cells with one or more firing fields, that match neurophysiological data about their development in juvenile rats. Both grid and place cells can develop by detecting, learning and remembering the most frequent and energetic co-occurrences of their inputs. The model's parsimonious properties include: similar ring attractor mechanisms process linear and angular path integration inputs that drive map learning; the same SOM mechanisms can learn grid cell and place cell receptive fields; and the learning of the dorsoventral organization of multiple spatial scale modules through medial entorhinal cortex to hippocampus (HC) may use mechanisms homologous to those for temporal learning through lateral entorhinal cortex to HC ('neural relativity'). The model clarifies how top-down HC-to-entorhinal attentional mechanisms may stabilize map learning, simulates how hippocampal inactivation may disrupt grid cells, and explains data about theta, beta and gamma oscillations. The article also compares the three main types of grid cell models in the light of recent data.

  8. Circulating polymerase chain reaction chips utilizing multiple-membrane activation

    NASA Astrophysics Data System (ADS)

    Wang, Chih-Hao; Chen, Yi-Yu; Liao, Chia-Sheng; Hsieh, Tsung-Min; Luo, Ching-Hsing; Wu, Jiunn-Jong; Lee, Huei-Huang; Lee, Gwo-Bin

    2007-02-01

    This paper reports a new micromachined, circulating, polymerase chain reaction (PCR) chip for nucleic acid amplification. The PCR chip is comprised of a microthermal control module and a polydimethylsiloxane (PDMS)-based microfluidic control module. The microthermal control modules are formed with three individual heating and temperature-sensing sections, each modulating a specific set temperature for denaturation, annealing and extension processes, respectively. Micro-pneumatic valves and multiple-membrane activations are used to form the microfluidic control module to transport sample fluids through three reaction regions. Compared with other PCR chips, the new chip is more compact in size, requires less time for heating and cooling processes, and has the capability to randomly adjust time ratios and cycle numbers depending on the PCR process. Experimental results showed that detection genes for two pathogens, Streptococcus pyogenes (S. pyogenes, 777 bps) and Streptococcus pneumoniae (S. pneumoniae, 273 bps), can be successfully amplified using the new circulating PCR chip. The minimum number of thermal cycles to amplify the DNA-based S. pyogenes for slab gel electrophoresis is 20 cycles with an initial concentration of 42.5 pg µl-1. Experimental data also revealed that a high reproducibility up to 98% could be achieved if the initial template concentration of the S. pyogenes was higher than 4 pg µl-1. The preliminary results of the current paper were presented at the 19th IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2006), Istanbul, Turkey, 22-26 January, 2006.

  9. 3D Filament Network Segmentation with Multiple Active Contours

    NASA Astrophysics Data System (ADS)

    Xu, Ting; Vavylonis, Dimitrios; Huang, Xiaolei

    2014-03-01

    Fluorescence microscopy is frequently used to study two and three dimensional network structures formed by cytoskeletal polymer fibers such as actin filaments and microtubules. While these cytoskeletal structures are often dilute enough to allow imaging of individual filaments or bundles of them, quantitative analysis of these images is challenging. To facilitate quantitative, reproducible and objective analysis of the image data, we developed a semi-automated method to extract actin networks and retrieve their topology in 3D. Our method uses multiple Stretching Open Active Contours (SOACs) that are automatically initialized at image intensity ridges and then evolve along the centerlines of filaments in the network. SOACs can merge, stop at junctions, and reconfigure with others to allow smooth crossing at junctions of filaments. The proposed approach is generally applicable to images of curvilinear networks with low SNR. We demonstrate its potential by extracting the centerlines of synthetic meshwork images, actin networks in 2D TIRF Microscopy images, and 3D actin cable meshworks of live fission yeast cells imaged by spinning disk confocal microscopy.

  10. 3D Actin Network Centerline Extraction with Multiple Active Contours

    PubMed Central

    Xu, Ting; Vavylonis, Dimitrios; Huang, Xiaolei

    2013-01-01

    Fluorescence microscopy is frequently used to study two and three dimensional network structures formed by cytoskeletal polymer fibers such as actin filaments and actin cables. While these cytoskeletal structures are often dilute enough to allow imaging of individual filaments or bundles of them, quantitative analysis of these images is challenging. To facilitate quantitative, reproducible and objective analysis of the image data, we propose a semi-automated method to extract actin networks and retrieve their topology in 3D. Our method uses multiple Stretching Open Active Contours (SOACs) that are automatically initialized at image intensity ridges and then evolve along the centerlines of filaments in the network. SOACs can merge, stop at junctions, and reconfigure with others to allow smooth crossing at junctions of filaments. The proposed approach is generally applicable to images of curvilinear networks with low SNR. We demonstrate its potential by extracting the centerlines of synthetic meshwork images, actin networks in 2D Total Internal Reflection Fluorescence Microscopy images, and 3D actin cable meshworks of live fission yeast cells imaged by spinning disk confocal microscopy. Quantitative evaluation of the method using synthetic images shows that for images with SNR above 5.0, the average vertex error measured by the distance between our result and ground truth is 1 voxel, and the average Hausdorff distance is below 10 voxels. PMID:24316442

  11. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity

    PubMed Central

    Dietsch, Gregory N.; Lu, Hailing; Yang, Yi; Morishima, Chihiro; Chow, Laura Q.; Disis, Mary L.; Hershberg, Robert M.

    2016-01-01

    VTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN). Activation of TLR8 enhances natural killer cell activation, increases antibody-dependent cell-mediated cytotoxicity, and induces Th1 polarizing cytokines. Here, we show that VTX-2337 stimulates the release of mature IL-1β and IL-18 from monocytic cells through coordinated actions on both TLR8 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome complex. In vitro, VTX-2337 primed monocytic cells to produce pro-IL-1β, pro-IL-18, and caspase-1, and also activated the NLRP3 inflammasome, thereby mediating the release of mature IL-1β family cytokines. Inhibition of caspase-1 blocked VTX-2337-mediated NLRP3 inflammasome activation, but had little impact on production of other TLR8-induced mediators such as TNFα. IL-18 activated natural killer cells and complemented other stimulatory pathways, including FcγRIII and NKG2D, resulting in IFNγ production and expression of CD107a. NLRP3 activation in vivo was confirmed by a dose-related increase in plasma IL-1β and IL-18 levels in cynomolgus monkeys administered VTX-2337. These results are highly relevant to clinical studies of combination VTX-2337/cetuximab treatment. Cetuximab, a clinically approved, epidermal growth factor receptor-specific monoclonal antibody, activates NK cells through interactions with FcγRIII and facilitates ADCC of tumor cells. Our preliminary findings from a Phase I open-label, dose-escalation, trial that enrolled 13 patients with recurrent or metastatic SCCHN show that patient NK cells become more responsive to stimulation by NKG2D or FcγRIII following VTX-2337 treatment. Together, these results indicate that TLR8 stimulation and inflammasome activation by VTX-2337 can complement FcγRIII engagement and may augment clinical responses in SCCHN

  12. Connecting multiple spatial scales to decode the population activity of grid cells.

    PubMed

    Stemmler, Martin; Mathis, Alexander; Herz, Andreas V M

    2015-12-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large-scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus. PMID:26824061

  13. Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity.

    PubMed

    Bernhardt, Paul V; Chin, Piao; Sharpe, Philip C; Richardson, Des R

    2007-08-14

    The potentially tridentate ligand 2-pyridinecarbaldehyde isonicotinoyl hydrazone (HPCIH) and its analogues are an emerging class of orally effective Fe chelators that show great promise for the treatment of Fe overload diseases. Herein, we present an extensive study of the Fe coordination chemistry of the HPCIH analogues including the first crystallographically characterised Fe(II) complex of these chelators. Unlike most other clinically effective Fe chelators, the HPCIH analogues bind Fe(II) and not Fe(III). In fact, these chelators form low-spin bis-ligand Fe(II) complexes, although NMR suggests that the complexes are close to the high-spin/low-spin crossover. All the Fe complexes show a high potential Fe(III/II) redox couple (> 500 mV vs. NHE) and cyclic voltammetry in aqueous or mixed aqueous/organic solvents is irreversible as a consequence of a rapid hydration reaction that occurs upon oxidation. A number of the HPCIH analogues show high activity at inducing Fe efflux from cells and also at preventing Fe uptake by cells from the serum Fe transport protein transferrin. As a class of ligands, these chelators are more effective at reducing Fe uptake from transferrin than inducing Fe mobilisation from cells. This may be related to their ability to intercept Fe(II) after its release from transferrin within the cell. Our studies indicate that their Fe chelation efficacy is due, at least in part, to the fact that these ligands and their Fe(II) complexes are neutral at physiological pH (7.4) and sufficiently lipophilic to permeate cell membranes. PMID:17893768

  14. Cooccurrence of problems in activity level, attention, psychosocial adjustment, reading and writing in children with developmental coordination disorder.

    PubMed

    Tseng, Mei-Hui; Howe, Tsu-Hsin; Chuang, I-Ching; Hsieh, Ching-Lin

    2007-12-01

    The purpose of this paper was to investigate the cooccurrence of problems in activity level, attention, reading, writing and psychosocial adjustment of children with developmental coordination disorder (DCD). A parent-report questionnaire, the Developmental Coordination Disorder Questionnaire - Chinese version (DCDQ-C), was used to screen first to third graders from 13 mainstream schools in Taipei. Two standardized motor tests were then administered to those who scored below 10% on the DCDQ-C. Tests of activity level, attention, reading, writing and psychosocial adjustment were then administered to this sample. Thirty-eight children identified as DCD, 32 as suspect for DCD and 82 as normal comparison were included in the final sample. Multivariate analysis of variance comparing the three groups (DCD, suspect DCD, and comparison) revealed that both children with DCD and suspect for DCD obtained significantly poorer scores on measures of attention and reading, and were more hyperactive than comparison children. Children with DCD and suspect for DCD were also reported to have more internalizing and social problems than children without motor problems. No significant differences, however, were noted between children with different degree of motor coordination problems (categorized as DCD and suspect for DCD) on any measure. Furthermore, a high percentage of children in both the DCD and suspect groups fell in the clinical range of attention, activity level and psychosocial adjustment problems. The results revealed a high risk for these problems in nonreferred children with motor coordination problems. The high percentage of clinical range behavioral problems warrants attention of clinicians who work with children with motor coordination difficulties to the need to promote early identification and referral.

  15. Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate

    PubMed Central

    Kimura-Yoshida, Chiharu; Yan, Kuo; Bormuth, Olga; Ding, Qiong; Nakanishi, Akiko; Sasaki, Takeshi; Hirakawa, Mika; Sumiyama, Kenta; Furuta, Yasuhide; Tarabykin, Victor; Matsuo, Isao; Okada, Norihiro

    2016-01-01

    Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution. PMID:27741242

  16. Redox-active porous coordination polymer based on trinuclear pivalate: Temperature-dependent crystal rearrangement and redox-behavior

    SciTech Connect

    Lytvynenko, Anton S.; Kiskin, Mikhail A.; Dorofeeva, Victoria N.; Mishura, Andrey M.; Titov, Vladimir E.; Kolotilov, Sergey V.; Eremenko, Igor L.; Novotortsev, Vladimir M.

    2015-03-15

    Linking of trinuclear pivalate Fe{sub 2}NiO(Piv){sub 6} (Piv=O{sub 2}CC(CH{sub 3}){sub 3}) by 2,6-bis(4-pyridyl)-4-(1-naphthyl)pyridine (L) resulted in formation of 1D-porous coordination polymer Fe{sub 2}NiO(Piv){sub 6}(L)·Solv, which was characterized in two forms: DMSO solvate Fe{sub 2}NiO(Piv){sub 6}(L)(DMSO)·2.5DMSO (1) or water solvate Fe{sub 2}NiO(Piv){sub 6}(L)(H{sub 2}O) (2). X-ray structure of 1 was determined. Crystal lattice of 1 at 160 K contained open channels, filled by captured solvent, while temperature growth to 296 K led to the crystal lattice rearrangement and formation of closed voids. Redox-behavior of 2 was studied by cyclic voltammetry for a solid compound, deposited on glassy-carbon electrode. Redox-activity of L preserved upon incorporation in the coordination polymer. The presence of pores in desolvated sample Fe{sub 2}NiO(Piv){sub 6}(L) was confirmed by the measurements of N{sub 2} and H{sub 2} adsorption at 77 K. Potential barriers of the different molecules diffusion through pores were estimated by the means of molecular mechanics. - Graphical abstract: Redox-behavior of 1D-porous coordination polymer Fe{sub 2}NiO(Piv){sub 6}(L)(H{sub 2}O) was studied by cyclic voltammetry in thin film, deposited on glassy-carbon electrode. Redox-activity of L preserved upon incorporation in the coordination polymer. Potential barriers of different molecules diffusion through pores were estimated by the means of molecular mechanics. - Highlights: • Porous 1D coordination polymer was synthesized. • Temperature growth led to pores closing due to crystal lattice rearrangement. • Redox-activity of ligand preserved upon incorporation into coordination polymer. • Redox-properties of solid coordination polymer were studied in thin film. • Diffusion barriers were evaluated by molecular mechanics.

  17. Tripyrrindione as a Redox-Active Ligand: Palladium(II) Coordination in Three Redox States.

    PubMed

    Gautam, Ritika; Loughrey, Jonathan J; Astashkin, Andrei V; Shearer, Jason; Tomat, Elisa

    2015-12-01

    The tripyrrin-1,14-dione scaffold of urinary pigment uroerythrin coordinates divalent palladium as a planar tridentate ligand. Spectroscopic, structural and computational investigations reveal that the tripyrrindione ligand binds as a dianionic radical, and the resulting complex is stable at room temperature. One-electron oxidation and reduction reactions do not alter the planar coordination sphere of palladium(II) and lead to the isolation of two additional complexes presenting different redox states of the ligand framework. Unaffected by stability problems common to tripyrrolic fragments, the tripyrrindione ligand offers a robust platform for ligand-based redox chemistry.

  18. Intermolecular C-H activation with an Ir-METAMORPhos piano-stool complex--multiple reaction steps at a reactive ligand.

    PubMed

    Oldenhof, S; Lutz, M; van der Vlugt, J I; Reek, J N H

    2015-10-21

    Substrate activation by means of a reactive ligand is a topic of much interest. Herein we describe a stoichiometric anti-Markovnikov C-N bond formation involving ligand reactivity in multiple steps along the reaction coordinate, including ligand assisted substrate (de)protonation and C-N bond formation, as illustrated by a combined experimental, spectroscopic and computational study. This affords a highly unusual four-membered iridacycle bearing an exo-cyclic C=C double bond.

  19. Intermolecular C-H activation with an Ir-METAMORPhos piano-stool complex--multiple reaction steps at a reactive ligand.

    PubMed

    Oldenhof, S; Lutz, M; van der Vlugt, J I; Reek, J N H

    2015-10-21

    Substrate activation by means of a reactive ligand is a topic of much interest. Herein we describe a stoichiometric anti-Markovnikov C-N bond formation involving ligand reactivity in multiple steps along the reaction coordinate, including ligand assisted substrate (de)protonation and C-N bond formation, as illustrated by a combined experimental, spectroscopic and computational study. This affords a highly unusual four-membered iridacycle bearing an exo-cyclic C=C double bond. PMID:26329519

  20. A new insight into the nature of seasonal variations in coordinate time series of GPS sites located near active faults

    NASA Astrophysics Data System (ADS)

    Trofimenko, Sergey V.; Bykov, Victor G.; Shestakov, Nikolay V.; Grib, Nikolay N.; Takahashi, Hiroaki

    2016-09-01

    This study provides new insights into the nature of seasonal variations in coordinate time series of GPS sites located near active faults and methods of their modeling. Monthly averaged coordinate time series were analyzed for several pairs of collocated GPS sites situated near the active fault intersection area, in close proximity to the central part of the northern boundary of the Amurian plate and the vicinity of the San Andreas Fault zone. It is concluded that the observed seasonal variations are best described by a breather function which is one of the solutions of the well-known sine-Gordon equation. The obtained results suggest that, in this case, the source of seasonal variations may be caused by the appearance of solitary strain waves in the fault intersection system, which may be qualitatively treated as standing waves of compression-extension of the geological medium. Based on statistical testing, the limits of applicability of the suggested model have been established.

  1. SATB1 Packages Densely Looped, Transcriptionally Active Chromatin for Coordinated Expression of Cytokine Genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    SATB1 (special AT-rich sequence binding protein 1) organizes cell type–specific nuclear architecture by anchoring specialized DNA sequences and recruiting chromatin remodeling factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4 and...

  2. Flexibility and Coordination among Acts of Visualization and Analysis in a Pattern Generalization Activity

    ERIC Educational Resources Information Center

    Nilsson, Per; Juter, Kristina

    2011-01-01

    This study aims at exploring processes of flexibility and coordination among acts of visualization and analysis in students' attempt to reach a general formula for a three-dimensional pattern generalizing task. The investigation draws on a case-study analysis of two 15-year-old girls working together on a task in which they are asked to calculate…

  3. Dominance of the proximal coordinate frame in determining the locations of hippocampal place cell activity during navigation.

    PubMed

    Siegel, Jennifer J; Neunuebel, Joshua P; Knierim, James J

    2008-01-01

    The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform a tone-initiated place-preference task on an open-field platform. To investigate whether place activity was bound to the room- or platform-based coordinate frame (or both), the platform was translated within the room at an "early" and at a "late" phase of task acquisition (Shift 1 and Shift 2). At both time points, CA1 and CA3 place cells demonstrated room-associated and/or platform-associated activity, or remapped in response to the platform shift. Shift 1 revealed place activity that reflected an interaction between a dominant platform-based (proximal) coordinate frame and a weaker room-based (distal) frame because many CA1 and CA3 place fields shifted to a location intermediate to the two reference frames. Shift 2 resulted in place activity that became more strongly bound to either the platform- or room-based coordinate frame, suggesting the emergence of two independent spatial frames of reference (with many more cells participating in platform-based than in room-based representations).

  4. Development of a database for prompt gamma-ray neutron activation analysis: Summary report of the third research coordination meeting

    SciTech Connect

    Lindstrom, Richard M.; Firestone, Richard B.; Pavi, ???

    2003-04-01

    The main discussions and conclusions from the Third Co-ordination Meeting on the Development of a Database for Prompt Gamma-ray Neutron Activation Analysis are summarized in this report. All results were reviewed in detail, and the final version of the TECDOC and the corresponding software were agreed upon and approved for preparation. Actions were formulated with the aim of completing the final version of the TECDOC and associated software by May 2003.

  5. Assisting Persons with Multiple Disabilities to Move through Simple Occupational Activities with Automatic Prompting

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Oliva, Doretta; Campodonico, Francesca; Groeneweg, Jop

    2008-01-01

    The present study assessed the possibility of assisting four persons with multiple disabilities to move through and perform simple occupational activities arranged within a room with the help of automatic prompting. The study involved two multiple probe designs across participants. The first multiple probe concerned the two participants with…

  6. Analysis of active neutron multiplicity data for Y-12 skull oxide samples

    SciTech Connect

    Krick, M.S.; Ensslin, N.; Ceo, R.N.; May, P.K.

    1996-09-01

    Previous work on active neutron multiplicity measurements and analyses is summarized. New active multiplicity measurements are described for samples of Y-12 skull oxide using an Active Well Coincidence Counter and MSR4 multiplicity electronics. Neutron multiplication values for the samples were determined from triples/doubles ratios. Neutron multiplication values were also obtained from Monte Carlo calculations using the MCNP code and the results compared with the experimental values. A calibration curve of AmLi source-sample coupling vs neutron multiplication was determined and used for active multiplicity assay of the skull oxides. The results are compared with those obtained from assay with the conventional calibration-curve technique, where the doubles rate is calibrated vs the {sup 235}U mass. The coupling-multiplication relationship determined for the skull oxides is compared with that determined earlier for pure high-enrichment uranium metal and pure uranium oxide. Conclusions are drawn about the application of active multiplicity techniques to uranium assay. Additional active multiplicity measurements and calculations are recommended.

  7. Act as NARSTO Management Coordinator and Conduct Research In Support of NARSTO Activities

    SciTech Connect

    Pennell, William T.

    2014-01-22

    This grant funded the position of NARSTO Management Coordinator. NARSTO was a public-private partnership with members from government, utilities, industry, and academe in Canada, the United States and Mexico. NARSTO planed and coordinated independently sponsored projects and tasks designed to identify and resolve policy-relevant science questions related to a) Anthropogenic and biogenic air-pollution sources and emissions, b) The complex physical and chemical processes affecting the accumulation of pollutants in the troposphere (including greenhouse gases and aerosols), c) The potential of certain pollutants to react and generate oxidants and fine particles in the troposphere, d) The development, intercomparison, and application of atmospheric models, e) The development of monitoring studies and methodologies needed to assess emission control effectiveness for selected greenhouse gases and aerosols, air pollutants and their precursors, and f) The attainment of the national air-quality and climate-stabilization goals and standards established by each member Nation

  8. Reproducibility of liver position using active breathing coordinator for liver cancer radiotherapy

    SciTech Connect

    Eccles, Cynthia; Brock, Kristy K.; Bissonnette, Jean-Pierre; Hawkins, Maria; Dawson, Laura A. . E-mail: laura.dawson@rmp.uhn.on.ca

    2006-03-01

    Purpose: To measure the intrabreath-hold liver motion and the intrafraction and interfraction reproducibility of liver position relative to vertebral bodies using an active breathing coordinator (ABC) in patients with unresectable liver cancer treated with hypofractionated stereotactic body radiation therapy (SBRT). Methods: Tolerability of ABC and organ motion during ABC was assessed using kV fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT scans in the ABC breath-hold position were acquired at simulation to estimate the volumetric intrafraction reproducibility of the liver relative to the vertebral bodies. In addition, preceding each radiation therapy fraction, with the liver immobilized using ABC, repeat anteroposterior (AP) megavoltage verification images were obtained. Off-line alignments were completed to determine intrafraction reproducibility (from repeat images obtained before one treatment) and interfraction reproducibility (from comparisons of the final image for each fraction with the AP) of diaphragm position relative to vertebral bodies. For each image set, the vertebral bodies were aligned, and the resultant craniocaudal (CC) offset in diaphragm position was measured. Liver position during ABC was also evaluated from kV fluoroscopy acquired at the time of simulation, kV fluoroscopy at the time of treatment, and from MV beam's-eye view movie loops acquired during treatment. Results: Twenty-one of 34 patients were screened to be suitable for ABC. The average free breathing range of these patients was 13 mm (range, 5-1 mm). Fluoroscopy revealed that the average maximal diaphragm motion during ABC breath-hold was 1.4 mm (range, 0-3.4 mm). The MV treatment movie loops confirmed diaphragm stability during treatment. For a measure of intrafraction reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in 14 patients was conducted. The average mean difference in the liver surface position was -0.9 mm, -0

  9. [The brain structures functional activity and aggression patients' multiple sclerosis].

    PubMed

    Reznikova, T N; Seliverstova, N A; Kataeva, G V; Aroev, R A; Il'ves, A G; Kuznetsova, A K

    2015-01-01

    The article is devoted to investigation of unconscious aggression in patients with multiple sclerosis. We carried out comparison of the relative assessments of metabolism speed of glucose (according to positron emission tomography) and indicators of unconscious aggression (in the Hand test). It is shown that an increased tendency to open aggression (unconscious aggression) in patients with multiple sclerosis, is mainly linked with a reduction in the functioning of different departments of the frontal lobes of the brain on the left and with changes of the metabolism speed of glucose in the structures of the limbic system of the left and right hemisphere. With increasing of unconscious aggression we observed decrease of glucose metabolism speed in certain areas of the lower and middle frontal gyrus.

  10. Study of Starburst/Activity/Interaction Phenomena based on the Multiple Byurakan-IRAS Galaxies

    NASA Astrophysics Data System (ADS)

    Harutyunyan, Gohar S.; Mickaelian, Areg M.

    2014-07-01

    The Byurakan-IRAS Galaxy (BIG) sample is the result of optical identifications of IRAS PSC sources at high-galactic latitudes using the First Byurakan Survey (FBS) low-dispersion spectra. Among the 1178 objects most are spiral galaxies and many have been proved to be AGN and starburst by spectroscopic observations, as well as there is a number of ULIRGs among these objects. BIG objects contain galaxy pairs, multiples, and small groups that are subject for study on the matter of the real IR-emitter in these systems. Given that these objects are powerful IR sources, they are considered as young systems indicating high rate of evolution and starburst activity exceeding 100 M o /yr. Spectroscopic observations show that all these systems are physical ones and we were able to measure the mutual distances and sizes for all components. Cross-correlations with the recent more accurate IR catalogues, such as 2MASS and WISE, as well as radio ones (NVSS, FIRST), provided accurate coordinates of the IR source and possibility to find the individual galaxy responsible for the IR. However, in almost half of the cases, IR position indicates the intermediate region between the components, which means that it comes from the system as a whole. Some more MW data have been matched to IR and radio to have an overall understanding on these systems. Given that these systems are mostly interacting/merging ones often containing AGN and most of them may be considered as powerful starbursts, it is possible to study starburst/activity/interaction phenomena and their interrelationship.

  11. Coordination of Mars Orbiting Assets to Support Entry, Descent, and Landing (EDL) Activities

    NASA Technical Reports Server (NTRS)

    Neelon, Joseph G.; Wallace, Mark; Craig, Lynn E.

    2004-01-01

    NASA policy requires continuous telecommunications with missions during the execution of their critical events, which implies constraints on where missions to other planets may land or inject into orbit. JPL is working to establish a telecommunications network at Mars to provide contact with inbound missions to Mars and assets that have landed on the Martian surface, thus reducing the constraints on where critical events may be performed. Coordination of network assets is required to cover an inbound mission's critical event, such as EDL. This paper describes the development of a tool to evaluate EDL coverage capability of Mars network assets over a specified launch date/arrival date space.

  12. Firefighters’ Physical Activity across Multiple Shifts of Planned Burn Work

    PubMed Central

    Chappel, Stephanie E.; Aisbett, Brad; Vincent, Grace E.; Ridgers, Nicola D.

    2016-01-01

    Little is currently known about the physical activity patterns of workers in physically demanding populations. The aims of this study were to (a) quantify firefighters’ physical activity and sedentary time within (2-h periods) and across planned burn shifts; and (b) examine whether firefighters’ activity levels during one shift or 2-h period was associated with their activity levels in the following shift or 2-h period. Thirty-four salaried firefighters (26 men, 8 women) wore an Actical accelerometer for 28 consecutive days. Time spent sedentary (SED) and in light- (LPA), moderate- (MPA) and vigorous-intensity physical activity (VPA) were derived using validated cut-points. Multilevel analyses (shift, participant) were conducted using generalised linear latent and mixed models. Firefighters spent the majority of a planned burn shift (average length 10.4 h) or 2-h period engaged in LPA (69% and 70%, respectively). No significant associations were observed between SED and physical activity levels between consecutive planned burned shifts or 2-h periods. The physical activity that a firefighter engaged in during one shift (or 2-h period) did not subsequently affect their physical activity levels in the subsequent shift (or 2-h period). Further research is needed to establish how workers in physically demanding populations are able to sustain their activity levels over long periods of time. PMID:27706057

  13. Participation in Physical Activity, Fitness, and Risk for Obesity in Children with Developmental Coordination Disorder: A Cross-cultural Study.

    PubMed

    Cermak, S A; Katz, N; Weintraub, N; Steinhart, S; Raz-Silbiger, S; Munoz, M; Lifshitz, N

    2015-12-01

    Decreased physical activity has been linked to poor fitness and obesity, resulting in increased risk for health concerns. The objective is to study the relationships between children's motor coordination and their physical activity, sedentary behaviour, fitness and weight status in a cross-cultural study in the United States and Israel. Participants included 118 children 6-11 years of age: 53 children with developmental coordination disorder (DCD) and 65 typical children. The US sample included 31 DCD children and 44 typical children. The Israeli sample included 22 DCD children and 21 typical children. Participants were assessed on Movement Assessment Battery for Children 2, strength test of the Bruininks-Oseretsky Test of Motor Proficiency 2 and Six-minute Walk Test and wore an accelerometer. Parents completed physical activity questionnaires and demographic information. Body mass index was calculated based on height and weight. Testing took place in two sessions. Findings are that in both Israel and the United States, children with DCD demonstrated significantly reduced physical activity, increased sedentary behaviour, poorer fitness and increased overweight compared with typical children. No significant differences were found for country. With relevance to clinical practice, fitness and obesity are major concerns for children with DCD in both countries. Inclusion of occupational therapy in health promotion for this population is critical. Additional studies with testers blind to group, larger samples and other countries are recommended.

  14. Participation in Physical Activity, Fitness, and Risk for Obesity in Children with Developmental Coordination Disorder: A Cross-cultural Study.

    PubMed

    Cermak, S A; Katz, N; Weintraub, N; Steinhart, S; Raz-Silbiger, S; Munoz, M; Lifshitz, N

    2015-12-01

    Decreased physical activity has been linked to poor fitness and obesity, resulting in increased risk for health concerns. The objective is to study the relationships between children's motor coordination and their physical activity, sedentary behaviour, fitness and weight status in a cross-cultural study in the United States and Israel. Participants included 118 children 6-11 years of age: 53 children with developmental coordination disorder (DCD) and 65 typical children. The US sample included 31 DCD children and 44 typical children. The Israeli sample included 22 DCD children and 21 typical children. Participants were assessed on Movement Assessment Battery for Children 2, strength test of the Bruininks-Oseretsky Test of Motor Proficiency 2 and Six-minute Walk Test and wore an accelerometer. Parents completed physical activity questionnaires and demographic information. Body mass index was calculated based on height and weight. Testing took place in two sessions. Findings are that in both Israel and the United States, children with DCD demonstrated significantly reduced physical activity, increased sedentary behaviour, poorer fitness and increased overweight compared with typical children. No significant differences were found for country. With relevance to clinical practice, fitness and obesity are major concerns for children with DCD in both countries. Inclusion of occupational therapy in health promotion for this population is critical. Additional studies with testers blind to group, larger samples and other countries are recommended. PMID:26123622

  15. Coordination of tongue activity during swallowing in mouth-breathing children.

    PubMed

    Knösel, Michael; Klein, Sabine; Bleckmann, Annalen; Engelke, Wilfried

    2012-09-01

    Habitual mouth breathing is often accompanied by habitual anterior tongue thrust, instead of a lip closure, in order to create the anterior seal necessary for the initiation of physiological deglutition. We tested the null hypothesis of no significant influence of oral maneuver and the use of oral screens on tongue coordination and position during deglutition in 29 subjects (age = 6-16; mean = 9.69 years; 13/16 female/male) with habitual open-mouth posture using intraoral polysensography. The target parameters for swallowing were swallowing-associated nasal airflow interruption (NAI) and coordination of tongue-palate contact during NAI. Conventional myofunctional maneuvers could be facilitated and made more efficient, in terms of increasing the numbers of favorable early tongue-palate contacts typical of somatic swallowing, if accompanied by the application of an oral screen. Habitual open-mouth breathing does not necessarily coincide with distinctively pronounced proportions of late tongue-palate contact.

  16. Angiogenic activity of sesamin through the activation of multiple signal pathways

    SciTech Connect

    Chung, Byung-Hee; Lee, Jung Joon; Kim, Jong-Dai; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Ha, Kwon-Soo; Kwon, Young-Geun; Kim, Young-Myeong

    2010-01-01

    The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125{sup FAK}-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

  17. Active Learning Handbook for the Multiple Intelligences Classroom. Shoebox Curriculum. K-12.

    ERIC Educational Resources Information Center

    Bellanca, James

    Helping students develop multiple intelligences and achieve content mastery requires teachers to design meaningful active learning experiences. Active learning uses the active engagement of the students' thinking processes in learning and applying knowledge. By designing active strategies that engage each student's strongest learning skills, a…

  18. Relationship between motor skills, participation in leisure activities and quality of life of children with Developmental Coordination Disorder: temporal aspects.

    PubMed

    Raz-Silbiger, S; Lifshitz, N; Katz, N; Steinhart, S; Cermak, S A; Weintraub, N

    2015-03-01

    The study examined the relationship between motor skills, participation in leisure activities and quality of life (QOL), within a temporal context (school year vs. summer vacation and school days vs. weekends). Parents of 22 children with Developmental Coordination Disorder (DCD) and of 55 typically developing children, aged 6-11, filled out two questionnaires relating to their children's participation in leisure activities (vigorous, moderate and sedentary) and QOL. The Movement Assessment Battery for Children-2 (MABC-2) was administered to their children. Results showed that among the children with DCD, balance scores positively correlated with participation in sedentary activities, and in both groups both balance and aiming and catching were related to the physical and school aspects of QOL. Furthermore, participation in vigorous activities in the summer was positively correlated with social and school QOL. In contrast, among typically developing children, participation in vigorous activities during the school year was negatively correlated with school QOL. Finally, in both groups, participation in sedentary activities during school days was negatively correlated with school QOL. These results suggest that the parents' perceptions of their children's QOL may be related to the level of activeness of the leisure activities but also to temporal aspects. Therefore, it is important that therapists and educators consider the temporal aspects, when consulting with parents and their children regarding participation in leisure activities.

  19. Large Roads Reduce Bat Activity across Multiple Species

    PubMed Central

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations. PMID:24823689

  20. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and NF-κB

    PubMed Central

    Min, Junxia; Zaslavsky, Alexander; Fedele, Giuseppe; McLaughlin, Sara K.; Reczek, Elizabeth E.; De Raedt, Thomas; Guney, Isil; Strochlic, David E.; Laura, E.; Beroukhim, Rameen; Bronson, Roderick T.; Ryeom, Sandra; Hahn, William C.; Loda, Massimo; Cichowski, Karen

    2010-01-01

    Metastasis is responsible for the majority of prostate cancer-related deaths; however, little is known about the molecular mechanisms that underlie this process. Here we identify an oncogene-tumor suppressor cascade that promotes prostate cancer initiation and metastasis by coordinately activating Ras and NF-κB. Specifically, we show that loss of the RasGAP gene DAB2IP induces metastatic prostate cancer in a murine model. Notably, DAB2IP functions as a signaling scaffold that coordinately regulates Ras and NF-κB through distinct domains to promote tumor initiation and metastasis, respectively. DAB2IP is suppressed in human prostate cancer where expression inversely correlates with tumor grade and predicts prognosis. Moreover, we report that epigenetic silencing of DAB2IP is a key mechanism by which the polycomb-group protein EZH2 activates Ras, NF-κB, and triggers metastasis. These studies define the mechanism by which two major pathways can be simultaneously activated in metastatic prostate cancer and establish EZH2 as a driver of metastasis. PMID:20154697

  1. Coordination sphere of the third metal site is essential to the activity and metal selectivity of alkaline phosphatases.

    PubMed

    Koutsioulis, Dimitris; Lyskowski, Andrzej; Mäki, Seija; Guthrie, Ellen; Feller, Georges; Bouriotis, Vassilis; Heikinheimo, Pirkko

    2010-01-01

    Alkaline phosphatases (APs) are commercially applied enzymes that catalyze the hydrolysis of phosphate monoesters by a reaction involving three active site metal ions. We have previously identified H135 as the key residue for controlling activity of the psychrophilic TAB5 AP (TAP). In this article, we describe three X-ray crystallographic structures on TAP variants H135E and H135D in complex with a variety of metal ions. The structural analysis is supported by thermodynamic and kinetic data. The AP catalysis essentially requires octahedral coordination in the M3 site, but stability is adjusted with the conformational freedom of the metal ion. Comparison with the mesophilic Escherichia coli, AP shows differences in the charge transfer network in providing the chemically optimal metal combination for catalysis. Our results provide explanation why the TAB5 and E. coli APs respond in an opposite way to mutagenesis in their active sites. They provide a lesson on chemical fine tuning and the importance of the second coordination sphere in defining metal specificity in enzymes. Understanding the framework of AP catalysis is essential in the efforts to design even more powerful tools for modern biotechnology. PMID:19916164

  2. Enzyme design from the bottom up: an active nickel electrocatalyst with a structured peptide outer coordination sphere.

    PubMed

    Reback, Matthew L; Buchko, Garry W; Kier, Brandon L; Ginovska-Pangovska, Bojana; Xiong, Yijia; Lense, Sheri; Hou, Jianbo; Roberts, John A S; Sorensen, Christina M; Raugei, Simone; Squier, Thomas C; Shaw, Wendy J

    2014-02-01

    Catalytic, peptide-containing metal complexes with a well-defined peptide structure have the potential to enhance molecular catalysts through an enzyme-like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide-based metal complex built upon the well-characterized hydrogen production catalyst [Ni(P(Ph)2N(Ph))2](2+) (P(Ph)2N(Ph)=1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane). The incorporated peptide maintains its β-hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide-based metal complex (≈100,000 s(-1)) is enhanced compared to the parent complex ([Ni(P(Ph)2N(APPA))2](2+); ≈50,500 s(-1)). The combination of an active molecular catalyst with a structured peptide provides a scaffold that permits the incorporation of features of an enzyme-like outer-coordination sphere necessary to create molecular electrocatalysts with enhanced functionality.

  3. Active Collisions in Altered Gravity Reveal Eye-Hand Coordination Strategies

    PubMed Central

    White, Olivier; Lefèvre, Philippe; Wing, Alan M.; Bracewell, R. Martyn; Thonnard, Jean-Louis

    2012-01-01

    Most object manipulation tasks involve a series of actions demarcated by mechanical contact events, and gaze is usually directed to the locations of these events as the task unfolds. Typically, gaze foveates the target 200 ms in advance of the contact. This strategy improves manual accuracy through visual feedback and the use of gaze-related signals to guide the hand/object. Many studies have investigated eye-hand coordination in experimental and natural tasks; most of them highlighted a strong link between eye movements and hand or object kinematics. In this experiment, we analyzed gaze strategies in a collision task but in a very challenging dynamical context. Participants performed collisions while they were exposed to alternating episodes of microgravity, hypergravity and normal gravity. First, by isolating the effects of inertia in microgravity, we found that peak hand acceleration marked the transition between two modes of grip force control. Participants exerted grip forces that paralleled load force profiles, and then increased grip up to a maximum shifted after the collision. Second, we found that the oculomotor strategy adapted visual feedback of the controlled object around the collision, as demonstrated by longer durations of fixation after collision in new gravitational environments. Finally, despite large variability of arm dynamics in altered gravity, we found that saccades were remarkably time-locked to the peak hand acceleration in all conditions. In conclusion, altered gravity allowed light to be shed on predictive mechanisms used by the central nervous system to coordinate gaze, hand and grip motor actions during a mixed task that involved transport of an object and high impact loads. PMID:22984488

  4. Active collisions in altered gravity reveal eye-hand coordination strategies.

    PubMed

    White, Olivier; Lefèvre, Philippe; Wing, Alan M; Bracewell, R Martyn; Thonnard, Jean-Louis

    2012-01-01

    Most object manipulation tasks involve a series of actions demarcated by mechanical contact events, and gaze is usually directed to the locations of these events as the task unfolds. Typically, gaze foveates the target 200 ms in advance of the contact. This strategy improves manual accuracy through visual feedback and the use of gaze-related signals to guide the hand/object. Many studies have investigated eye-hand coordination in experimental and natural tasks; most of them highlighted a strong link between eye movements and hand or object kinematics. In this experiment, we analyzed gaze strategies in a collision task but in a very challenging dynamical context. Participants performed collisions while they were exposed to alternating episodes of microgravity, hypergravity and normal gravity. First, by isolating the effects of inertia in microgravity, we found that peak hand acceleration marked the transition between two modes of grip force control. Participants exerted grip forces that paralleled load force profiles, and then increased grip up to a maximum shifted after the collision. Second, we found that the oculomotor strategy adapted visual feedback of the controlled object around the collision, as demonstrated by longer durations of fixation after collision in new gravitational environments. Finally, despite large variability of arm dynamics in altered gravity, we found that saccades were remarkably time-locked to the peak hand acceleration in all conditions. In conclusion, altered gravity allowed light to be shed on predictive mechanisms used by the central nervous system to coordinate gaze, hand and grip motor actions during a mixed task that involved transport of an object and high impact loads.

  5. Endocrine disruptor activity of multiple environmental food chain contaminants.

    PubMed

    Wielogórska, E; Elliott, C T; Danaher, M; Connolly, L

    2015-02-01

    Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation. Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens( n = 3), UV filters (n = 6), phthalates (n = 4) and a metabolite, pyrethroids (n = 9) and their metabolites (n = 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17b-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

  6. Multiple forms of acid phosphatase activity in Gaucher's disease.

    PubMed

    Chambers, J P; Peters, S P; Glew, R H; Lee, R E; McCafferty, L R; Mercer, D W; Wenger, D A

    1978-07-01

    Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to

  7. Understanding physical activity and motivations for children with developmental coordination disorder: an investigation using the theory of planned behavior.

    PubMed

    Kwan, Matthew Y W; Cairney, John; Hay, John A; Faught, Brent E

    2013-11-01

    Developmental coordination disorder (DCD) is a neurodevelopmental condition, affecting approximately 5-6% of children. Previous research has consistently found children with DCD being less physically active compared to typically-developing (TD) children; however, the psychosocial factors associated with physical activity for children with DCD are poorly understood. The purpose of this study was to examine how theory-based physical activity cognitions impacts physical activity behaviors for children with and without DCD. Participants included a sample of boys (N=61, Mage=13.25 ±.46) with DCD (n=19) and without DCD (n=42), drawn from a larger prospective cohort study. A questionnaire with psychosocial measures was first administered, and accelerometers were used to assess their physical activity behavior over the subsequent week. Findings indicate that DCD was significantly associated with lower physical activity (F(1,58)=6.51, p<.05), and poorer physical activity cognitions (F(4,56) Wilks Lambda=2.78, p<.05). Meditational analyses found attitudes (B=.23, p<.05) and subjective norms (B=.31, p<.05) partially mediating the relationship between DCD and physical activity. Overall, this study further confirms that the activity deficit that exists among boys with DCD, and that the relationship is partially mediated through some physical activity cognitions. Interventions should target the perceived approval of influential people, and the personal evaluations of physical activity for boys with motoric difficulties. These findings further emphasizes the discrepancy in physical activity that exist between boys with DCD and TD boys, and highlight the need to better understand the psychological factors related to physical activity for children with DCD.

  8. Beyond the Active Site: The Impact of the Outer Coordination Sphere on Electrocatalysts for Hydrogen Production and Oxidation

    SciTech Connect

    Ginovska-Pangovska, Bojana; Dutta, Arnab; Reback, Matthew L.; Linehan, John C.; Shaw, Wendy J.

    2014-08-19

    Hydrogenase enzymes provide inspiration for investigations of molecular catalysts utilizing structural and functional mimics of the active site. However, the resulting active site mimics cannot match the combination of high rates and low overpotentials of the enzyme, suggesting that the rest of the protein scaffold, i.e., the outer coordination sphere, is necessary for the efficiency of hydrogenase. Therefore, inclusion of outer coordination sphere elements onto molecular catalysts may enable us to achieve and ultimately surpass the overall enzymatic efficiency. In an effort to identify and include the missing enzymatic features, there has been recent effort to understand the effect of outer coordination sphere elements on molecular catalysts for hydrogen oxidation and production. Our focus has been to utilize amino acid or peptide based scaffolds on an active functional mimic for hydrogen oxidation and production, [Ni(PR2NR’2)2]2+. This bottom-up approach, i.e, building an outer coordination sphere around a functional molecular catalyst, has allowed us to evaluate individual contributions to catalysis, including enhancing proton movement, concentrating substrate and introducing structural features to control reactivity. Collectively, these studies have resulted in catalysts that can operate faster, can operate at lower overpotentials, have enhanced water solubility, and/or can provide more stability to oxygen or extreme conditions such as strongly acidic or basic conditions than their unmodified parent complexes. Common mechanisms have yet to be defined to predictably control these processes but our growing knowledge in this area is essential for the eventual mimicry of enzymes for developing efficient molecular catalysts for practical use. This account reviews previously published work supported by the US DOE Basic Energy Sciences (BES), Physical Bioscience program, the Office of Science Early Career Research Program through the USDOE, BES, the Center for

  9. Activated G Protein Gαs Samples Multiple Endomembrane Compartments.

    PubMed

    Martin, Brent R; Lambert, Nevin A

    2016-09-23

    Heterotrimeric G proteins are localized to the plasma membrane where they transduce extracellular signals to intracellular effectors. G proteins also act at intracellular locations, and can translocate between cellular compartments. For example, Gαs can leave the plasma membrane and move to the cell interior after activation. However, the mechanism of Gαs translocation and its intracellular destination are not known. Here we use bioluminescence resonance energy transfer (BRET) to show that after activation, Gαs rapidly associates with the endoplasmic reticulum, mitochondria, and endosomes, consistent with indiscriminate sampling of intracellular membranes from the cytosol rather than transport via a specific vesicular pathway. The primary source of Gαs for endosomal compartments is constitutive endocytosis rather than activity-dependent internalization. Recycling of Gαs to the plasma membrane is complete 25 min after stimulation is discontinued. We also show that an acylation-deacylation cycle is important for the steady-state localization of Gαs at the plasma membrane, but our results do not support a role for deacylation in activity-dependent Gαs internalization. PMID:27528603

  10. CD4+ T cell activation in multiple sclerosis.

    PubMed

    Verselis, S J; Goust, J M

    1987-02-01

    Interleukin-2 (IL-2) production by CD4-enriched T cells from multiple sclerosis (MS) patients and normal individuals stimulated with concanavalin A (conA) and/or autologous and allogeneic B lymphoid cell lines (B-LCL) was evaluated 24, 48 and 96 h after stimulation. ConA-stimulated CD4+ cells from MS patients did not produce significantly more IL-2 than normal CD4+ cells. In contrast, autologous B-LCL-induced IL-2 production by MS CD4+ cells significantly (P = 0.026) exceeded that produced by normal CD4+ cells identically stimulated after 24 h in culture. Differences in IL-2 production by CD4+ cells from MS patients reached highest significance using allogeneic B-LCL, whose stimulatory capacity was similar, whether established from normal individuals or MS patients. This increased IL-2 production in response to B-LCL may represent a supranormal response of CD4+ cells from MS patients to class II major histocompatibility (MHC)-associated stimuli. It suggests that the deficiency of suppressor T cell functions postulated to play a role in MS does not arise from a lack of IL-2 induction and might indicate that bursts of IL-2 production could play a role in MS. PMID:3492511

  11. p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.

    PubMed

    Huang, Wayne; Zhou, Zikai; Asrar, Suhail; Henkelman, Mark; Xie, Wei; Jia, Zhengping

    2011-02-01

    The molecular mechanisms that coordinate postnatal brain enlargement, synaptic properties, and cognition remain an enigma. Here, we demonstrate that neuronal complexity controlled by p21-activated kinases (PAKs) is a key determinant for postnatal brain enlargement and synaptic properties. We showed that double-knockout (DK) mice lacking both PAK1 and PAK3 were born healthy, with normal brain size and structure, but severely impaired in postnatal brain growth, resulting in a dramatic reduction in brain volume. Remarkably, the reduced brain size was accompanied by minimal changes in total cell count, due to a significant increase in cell density. However, the DK neurons have smaller soma, markedly simplified dendritic arbors/axons, and reduced synapse density. Surprisingly, the DK mice had elevated basal synaptic responses due to enhanced individual synaptic potency but were severely impaired in bidirectional synaptic plasticity. The actions of PAK1 and PAK3 are possibly mediated by cofilin-dependent actin regulation, because the activity of cofilin and the properties of actin filaments were altered in the DK mice. These results reveal an essential in vivo role of PAK1 and PAK3 in coordinating neuronal complexity and synaptic properties and highlight the critical importance of dendrite/axon growth in dictating postnatal brain growth and attainment of normal brain size and function.

  12. Methylene bridge regulated geometrical preferences of ligands in cobalt(III) coordination chemistry and phenoxazinone synthase mimicking activity.

    PubMed

    Panja, Anangamohan; Shyamal, Milan; Saha, Amrita; Mandal, Tarun Kanti

    2014-04-14

    Two new azide bound cobalt(III) complexes, [Co(L(1))(N3)3] (fac-1) and [Co(L(2))(N3)3] (mer-2), where L(1) is bis(2-pyridylmethyl)amine and L(2) is (2-pyridylmethyl)(2-pyridylethyl)amine, derived from tridentate reduced Schiff-base ligands have been reported. Interestingly, a methylene bridge regulated preferential coordination mode of ligands is noticed in their crystal structures: it is found in a facial arrangement in fac-1 and has a meridional disposition in mer-2. Both complexes show phenoxazinone synthase-like activity and the role of the structural factor on the catalytic activity is also explored. Moreover, the easily reducible cobalt(III) center in mer-2 favors the oxidation of o-aminophenol. The ESI-MS positive spectra together with UV-vis spectroscopy clearly suggest the formation of a catalyst-substrate adduct by substitution of the coordinated azide ions in the catalytic cycle.

  13. Neutron Flux Spectra Determination by Multiple Foil Activation - Iterative Method.

    1994-07-08

    Version 00 Neutron energy spectra are determined by an analysis of experimental activation detector data. As with the original CCC-112/SAND-II program, which was developed at Air Force Weapons Laboratory, this code system consists of four modules, CSTAPE, SLACTS, SLATPE, and SANDII. The first three modules pre-process the dosimetry cross sections and the trial function spectrum library. The last module, SANDII, actually performs the iterative spectrum characterization.

  14. Multiple forms of endopeptidase activity from jojoba seeds.

    PubMed

    Wolf, M J; Storey, R D

    1990-01-01

    The cotyledons of 27 day post-germination jojoba seedlings (Simmondsia chinensis) contained five distinct endopeptidase activities separable by DEAE Bio-Gel and CM-cellulose ion exchange chromatography. The endopeptidases were purified 108- to 266-fold and their individuality was confirmed by activity-specific assays in native acrylamide gels along with differences in their Mr and catalytic properties. The five endopeptidases, which showed activity on model substrates and protein, were named EP Ia, EP Ib, EP II, EP III and EP IV. EP Ia was a serine proteinase with a pH optimum of ca 8 and Mr of 58,000. EP Ib, II and III were discrete cysteine proteinases showing pH optima of ca 6.8, 6.0 and 5.4 and Mr of 41,000, 47,000 and 35,000 respectively. EP IV was an aspartic acid proteinase with a ca pH optimum of 3.5 and Mr of 33,000.

  15. Multiple microbial activities for volatile organic compounds reduction by biofiltration.

    PubMed

    Civilini, Marcello

    2006-07-01

    In the northeast of Italy, high volatile organic carbon (VOC) emissions originate from small-medium companies producing furniture. In these conditions it is difficult to propose a single, efficient, and economic system to reduce pollution. Among the various choices, the biofiltration method could be a good solution, because microbial populations possess multiple VOC degradation potentials used to oxidize these compounds to CO2. Starting from the air emissions of a typical industrial wood-painting plant, a series of experiments studied in vitro microbial degradation of each individual VOC. Isolated strains were then added to a laboratory-scale biofiltration apparatus filled with an organic matrix, and the different VOC behavior demonstrated the potential of single and/or synergic microbial removal actions. When a single substrate was fed, the removal efficiency of a Pseudomonas aeruginosa inoculated reactor was 1.1, 1.17, and 0.33 g m(-3) hr(-1), respectively, for xylene, toluene, and ethoxy propyl acetate. A VOC mixture composed of butyl acetate, ethyl acetate, diacetin alcohol, ethoxy propanol acetate, methyl ethyl ketone, methyl isobutyl ketone, toluene, and xylene was then fed into a 2-m(3) reactor treating 100 m3 hr(-1) of contaminated air. The reactor was filled with the same mixture of organic matrix, enriched with all of the isolated strains together. During reactor study, different VOC loading rates were used, and the behavior was evaluated continuously. After a short acclimation period, the removal efficiency was > 65% at VOC load of 150-200 g m(-3) hr(-1). Quantification of removal efficiencies and VOC speciation confirmed the relationship among removal efficiencies, compound biodegradability, and the dynamic transport of each mixture component within the organic matrix. Samples of the fixed bed were withdrawn at different intervals and the heterogeneous microbial community evaluated for both total and differential compound counts. PMID:16878585

  16. Multiple RNase H activities in mammalian type C retravirus lysates.

    PubMed Central

    Gerard, G F

    1978-01-01

    Lysates of Moloney murine sarcoma-leukemia virus [M-MSV(MLV)], a virus complex grown in the rat cell line 78A-1, were found to contain three RNase H species separable by polycytidylic acid[poly(C)]-agarose chromatography. RNase H activity (RNase H I) associated with RNA-directed DNA polymerase eluted at 0.23 M KCI from poly(C)-agarose. RNase H II, which eluted from poly(C)-agarose at 0.12 M KCI and was not associated with DNA polymerase activity, was shown to be identical to an RNase H species (designated RNase H II) previously isolated from M-MSV(MLV) by a different procedure (G. F. Gerard and D. P. Grandgenett, J. Virol. 15:785-797, 1975). M-MSV(MLV) RNase H II was established to be a random exohybridase that requires free-chain termini in its hybrid substrate for activity. Lysates of Rickard feline leukemia virus also contained RNase H activity not associated with DNA polymerase activity that eluted from poly(C)-agarose at 0.12 M KCl. A third species of enzyme from M-MSV(MLV) lysates, called RNase H III, did not bind to poly(C)-agarose in 0.06 M KCl. RNase H III was purified from lysates of M-MSV(MLV) and M-MLV (grown in mouse cells) by sequential chromatography on poly(C)-agarose, DEAE-cellulose, phosphocellulose, and polyuridylic acid-Sepharose. Purified RNase H III (i) was free of any associated DNA polymerase activity, (ii) had an apparent molecular weight of 30,000 determined by Sephadex G-100 gel filtration, (iii) had an absolute requirement for Mn2+ (1 mM optimum) for the degradation of [3H](A)n.(dT)n, (iv) was inhibited by the presence of any salt in reaction mixtures, and (v) was endoribonucleolytic in its mode of action as indicated by the size distribution of limited degradation products of [3H](A)n.(dT)n. RNase H III was inhibited by antisera prepared against Rauscher MLV and simian sarcoma virus reverse transcriptase, and the quantity of RNase H III and RNase H I present in lysates of M-MLV were reduced and increased proportionately if virus was

  17. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  18. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  19. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  20. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  1. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  2. Coordinated Regulation of PPARγ Expression and Activity through Control of Chromatin Structure in Adipogenesis and Obesity

    PubMed Central

    Eeckhoute, Jérôme; Oger, Frédérik; Staels, Bart; Lefebvre, Philippe

    2012-01-01

    The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is required for differentiation and function of mature adipocytes. Its expression is induced during adipogenesis where it plays a key role in establishing the transcriptome of terminally differentiated white fat cells. Here, we review findings indicating that PPARγ expression and activity are intricately regulated through control of chromatin structure. Hierarchical and combinatorial activation of transcription factors, noncoding RNAs, and chromatin remodelers allows for temporally controlled expression of PPARγ and its target genes through sequential chromatin remodelling. In obesity, these regulatory pathways may be altered and lead to modified PPARγ activity. PMID:22991504

  3. In Vitro Antihepatoma Activity of Novel 3D-Copper Cyanide Supramolecular Coordination Polymers.

    PubMed

    Darwish, Noura M; Sultan, Ahmed S; Malki, Ahmed M; Khamis, Hossam; El-Ziady, Mohamed

    2016-09-01

    This study aimed to investigate the inhibitory effect of novel 3D-organocopper supramolecular coordination polymers (SCPs) on the invasive potential of HepG2 cells. Chemoprevention could represent an important means to inhibit the process of hepatocarcinogenesis. The inhibitory effect of an SCP compound on the proliferation of HepG2 hepatoma cells was evaluated by cell vibility assay. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of the SCP compound on phosphorylated ERK1/2, Bcl-2, and β-catenin protein expression of HepG2 cells was analyzed by Western blot. The SCP compound exerted an inhibitory effect on HepG2 cell proliferation in a dose-dependent manner. This inhibitory effect was confirmed by examination of cell morphology and DNA fragmentation. Furthermore, Western blot analysis revealed that phosphorylated ERK1/2 and β-catenin protein expression was inhibited after 24 h of treatment with the SCP compound, and that this event was associated with decreased Bcl-2 expression. We concluded that SCP can effectively inhibit the invasive potential of the ERK signaling pathway in HepG2 cells by altering apoptosis and by inhibiting Bcl-2 and β-catenin, which may play a significant role in this process.

  4. Transcription factors of Lotus: regulation of isoflavonoid biosynthesis requires coordinated changes in transcription factor activity.

    PubMed

    Shelton, Dale; Stranne, Maria; Mikkelsen, Lisbeth; Pakseresht, Nima; Welham, Tracey; Hiraka, Hideki; Tabata, Satoshi; Sato, Shusei; Paquette, Suzanne; Wang, Trevor L; Martin, Cathie; Bailey, Paul

    2012-06-01

    Isoflavonoids are a class of phenylpropanoids made by legumes, and consumption of dietary isoflavonoids confers benefits to human health. Our aim is to understand the regulation of isoflavonoid biosynthesis. Many studies have shown the importance of transcription factors in regulating the transcription of one or more genes encoding enzymes in phenylpropanoid metabolism. In this study, we coupled bioinformatics and coexpression analysis to identify candidate genes encoding transcription factors involved in regulating isoflavonoid biosynthesis in Lotus (Lotus japonicus). Genes encoding proteins belonging to 39 of the main transcription factor families were examined by microarray analysis of RNA from leaf tissue that had been elicited with glutathione. Phylogenetic analyses of each transcription factor family were used to identify subgroups of proteins that were specific to L. japonicus or closely related to known regulators of the phenylpropanoid pathway in other species. R2R3MYB subgroup 2 genes showed increased expression after treatment with glutathione. One member of this subgroup, LjMYB14, was constitutively overexpressed in L. japonicus and induced the expression of at least 12 genes that encoded enzymes in the general phenylpropanoid and isoflavonoid pathways. A distinct set of six R2R3MYB subgroup 2-like genes was identified. We suggest that these subgroup 2 sister group proteins and those belonging to the main subgroup 2 have roles in inducing isoflavonoid biosynthesis. The induction of isoflavonoid production in L. japonicus also involves the coordinated down-regulation of competing biosynthetic pathways by changing the expression of other transcription factors. PMID:22529285

  5. Electronic, optical, and computational studies of a redox-active napthalenediimide-based coordination polymer.

    PubMed

    Leong, Chanel F; Chan, Bun; Faust, Thomas B; Turner, Peter; D'Alessandro, Deanna M

    2013-12-16

    The new one-dimensional coordination framework (Zn(DMF)NO3)2(NDC)(DPMNI), where NDC = 2,6-naphthalenedicarboxylate and DPMNI = N,N'-bis(4-pyridylmethyl)-1,4,5,8-naphthalenetetracarboxydiimide, which has been crystallographically characterized, exhibits two redox-accessible states due to the successive reduction of the naphthalenediimide (NDI) ligand core. Solid-state electrochemical and vis-near-IR spectroelectrochemical measurements coupled with density functional theory (DFT) calculations enabled the origins of the optical transitions in the spectra of the monoradical anion and dianion states of the material to be assigned. Electron paramagnetic resonance (EPR) spectroscopy revealed that the paramagnetic radical anion state of the DPMNI core could be accessed upon broad-spectrum white light irradiation of the material, revealing a long-lived excited state, possibly stabilized by charge delocalization which arises from extensive π-π* stacking interactions between alternating NDC and NDI aromatic cores which are separated by a distance of 3.580(2) Å. PMID:24283401

  6. Mixed ligand coordination polymers with flexible bis-imidazole linker and angular sulfonyldibenzoate: Crystal structure, photoluminescence and photocatalytic activity

    SciTech Connect

    Bisht, Kamal Kumar; Rachuri, Yadagiri; Parmar, Bhavesh; Suresh, Eringathodi

    2014-05-01

    Four ternary coordination polymers (CPs) namely, ([Ni(SDB)(BITMB)(H{sub 2}O)]·H{sub 2}O){sub n} (CP1), ([Cd(SDB)(BITMB) (H{sub 2}O)]·(THF)(H{sub 2}O)){sub n} (CP2), ([Zn{sub 2}(SDB){sub 2}(BITMB)]·(THF){sub 2}){sub n} (CP3) and ([Co{sub 2}(SDB){sub 2}(BITMB)]·(Dioxane){sub 3}){sub n} (CP4) composed of angular dicarboxylate SDB (4,4'-sulfonyldibenzoate) and N-donor BITMB (1,3-bis(imidazol-1-ylmethyl)-2,4,6-trimethyl benzene) have been synthesized by solvothermal reactions and characterized by single crystal X-ray diffraction and other physico-chemical techniques. CP1 possesses one-dimensional ribbon type metal–organic motifs glued together by H-bonds and π⋯π interactions, whereas CP2–CP4, exhibit non-interpenetrated sql networks supported by weak supramolecular interactions. Structural diversity of these CPs can be attributed to the coordination geometry adopted by the metal nodes, versatile coordination modes of SDB and conformational flexibility of BITMB. Solid state luminescence properties of CP1–CP4 were explored. Photocatalytic performance of all CPs for the decomposition of metanil yellow by dilute hydrogen peroxide in the presence of visible light was also investigated. 25–83% dye removal from aqueous solutions in the presence of CP1–CP4 was observed. - Graphical abstract: Four new ternary transition metal CPs have been hydrothermally prepared and their structural aspects as well as photocatalytic activity for decolourization of metanil yellow (MY) dye have been investigated. - Highlights: • Four ternary coordination polymers containing Ni, Cd, Zn and Co center are prepared. • Crystal structure and thermal stability of all four CPs has been described. • PL and diffuse reflectance spectra of synthesized CPs have also been examined. • Band gap values suggest semiconducting behavior of prepared CPs. • Photocatalytic activity of CPs for oxidative degradation of metanil yellow is studied.

  7. Coordination challenges for autonomous spacecraft

    NASA Technical Reports Server (NTRS)

    Clement, B. J.; Barrett, A.

    2002-01-01

    While past flight projects involved a single spacecraft in isolation, over forty proposed future missions involve multiple coordinated spacecraft. This paper presents characteristics of such missions in terms of properties of the phenomena being measured as well as the rationale for using multiple spacecraft. We describe the coordination problems associated with operating these missions and identify needed technologies.

  8. The Long and the Short of It: Comments on Multiple Timescale Studies of Human Activity.

    ERIC Educational Resources Information Center

    Lemke, Jay L.

    2001-01-01

    Comments on four articles in a special issue of the Journal of the Learning Sciences on methodology in learning sciences. Analyzes the articles within a general model seeking to analyze human activity across multiple time scales. (Author/MM)

  9. Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

    ERIC Educational Resources Information Center

    Motl, Robert W.; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S.

    2009-01-01

    Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

  10. Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation.

    PubMed

    Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Lasserre, Rémi; Agüera-Gonzalez, Sonia; Cuche, Céline; Danckaert, Anne; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

    2016-06-01

    The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation.

  11. Efficient Multiple Object Tracking Using Mutually Repulsive Active Membranes

    PubMed Central

    Deng, Yi; Coen, Philip; Sun, Mingzhai; Shaevitz, Joshua W.

    2013-01-01

    Studies of social and group behavior in interacting organisms require high-throughput analysis of the motion of a large number of individual subjects. Computer vision techniques offer solutions to specific tracking problems, and allow automated and efficient tracking with minimal human intervention. In this work, we adopt the open active contour model to track the trajectories of moving objects at high density. We add repulsive interactions between open contours to the original model, treat the trajectories as an extrusion in the temporal dimension, and show applications to two tracking problems. The walking behavior of Drosophila is studied at different population density and gender composition. We demonstrate that individual male flies have distinct walking signatures, and that the social interaction between flies in a mixed gender arena is gender specific. We also apply our model to studies of trajectories of gliding Myxococcus xanthus bacteria at high density. We examine the individual gliding behavioral statistics in terms of the gliding speed distribution. Using these two examples at very distinctive spatial scales, we illustrate the use of our algorithm on tracking both short rigid bodies (Drosophila) and long flexible objects (Myxococcus xanthus). Our repulsive active membrane model reaches error rates better than per fly per second for Drosophila tracking and comparable results for Myxococcus xanthus. PMID:23799046

  12. Inferring Human Activity in Mobile Devices by Computing Multiple Contexts

    PubMed Central

    Chen, Ruizhi; Chu, Tianxing; Liu, Keqiang; Liu, Jingbin; Chen, Yuwei

    2015-01-01

    This paper introduces a framework for inferring human activities in mobile devices by computing spatial contexts, temporal contexts, spatiotemporal contexts, and user contexts. A spatial context is a significant location that is defined as a geofence, which can be a node associated with a circle, or a polygon; a temporal context contains time-related information that can be e.g., a local time tag, a time difference between geographical locations, or a timespan; a spatiotemporal context is defined as a dwelling length at a particular spatial context; and a user context includes user-related information that can be the user’s mobility contexts, environmental contexts, psychological contexts or social contexts. Using the measurements of the built-in sensors and radio signals in mobile devices, we can snapshot a contextual tuple for every second including aforementioned contexts. Giving a contextual tuple, the framework evaluates the posteriori probability of each candidate activity in real-time using a Naïve Bayes classifier. A large dataset containing 710,436 contextual tuples has been recorded for one week from an experiment carried out at Texas A&M University Corpus Christi with three participants. The test results demonstrate that the multi-context solution significantly outperforms the spatial-context-only solution. A classification accuracy of 61.7% is achieved for the spatial-context-only solution, while 88.8% is achieved for the multi-context solution. PMID:26343665

  13. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways.

  14. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways. PMID:27531451

  15. The loading of coordination complex modified polyoxometalate nanobelts on activated carbon fiber: a feasible strategy to obtain visible light active and highly efficient polyoxometalate based photocatalysts.

    PubMed

    Lu, Tingting; Xu, Xinxin; Li, Huili; Li, Zhenyu; Zhang, Xia; Ou, Jinzhao; Mei, Mingliang

    2015-02-01

    To enhance the photocatalytic properties of coordination complex modified polyoxometalates (CC/POMs) in the visible light region, its nanobelts (CC/POMNBs) were loaded on activated carbon fiber (ACF) through a simple colloidal blending process. The resulting coordination complex modified polyoxometalate nanobelts loaded activated carbon fiber composite materials (CC/POMNBs/ACF) exhibited dramatic photocatalytic activity for the degradation of rhodamine B (RhB) under visible light irradiation. Optical and electrochemical methods illustrated the enhanced photocatalytic activity of CC/POMNBs/ACF, which originates from the high separation efficiency of the photogenerated electrons and holes on the interface of the CC/POMNBs and ACF, which results from the synergistic effects between them. In the composite material, the role of ACF could be described as a photosensitizer and a good electron transporter. Furthermore, the influence of the mass ratio between the CC/POMNBs and ACF on the photocatalytic performance of the resulting composite material was discussed, and an ideal value to obtain highly efficient photocatalysts was obtained. The results suggested that the loading of CC/POMNBs on the surface of ACF would be a feasible strategy to enhance their photocatalytic activity.

  16. Scientific coordination of activities for university participation in mission to planet Earth

    NASA Technical Reports Server (NTRS)

    Kalb, Michael W.

    1994-01-01

    This report describes Universities Space Research Association (USRA) activities in support of the University Participation in Mission to Planet Earth. Specifically it addresses the following areas: personnel assigned to the effort, travel, consultant participants, technical progress, and contract spending.

  17. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes.

    PubMed

    Lobel, Lior; Herskovits, Anat A

    2016-02-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY's regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

  18. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes

    PubMed Central

    Lobel, Lior; Herskovits, Anat A.

    2016-01-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY’s regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

  19. Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis.

    PubMed

    Kahnert, Antje; Seiler, Peter; Stein, Maik; Bandermann, Silke; Hahnke, Karin; Mollenkopf, Hans; Kaufmann, Stefan H E

    2006-03-01

    A potent Th1 immune response is critical to the control of tuberculosis. The impact of an additive Th2 response on the course of disease has so far been insufficiently characterized, despite increased morbidity after co-infection with Mycobacterium tuberculosis and Th2-eliciting helminths and possible involvement of Th2 polarization in reactivation of latent tuberculosis. Here, we describe the gene expression profile of murine bone marrow-derived macrophages alternatively activated by IL-4 in response to infection with M. tuberculosis. Comparison of transcriptional profiles of infected IL-4- and IFN-gamma-activated macrophages revealed delayed and partially diminished responses to intracellular bacteria in alternatively activated macrophages, characterized by reduced exposure to nitrosative stress and increased iron availability, respectively. Alternative activation of host macrophages correlated with elevated expression of the M. tuberculosis iron storage protein bacterioferritin as well as reduced expression of the mycobactin synthesis genes mbtI and mbtJ. The extracellular matrix-remodeling enzyme matrix metalloproteinase (MMP)-12 was induced in alternatively activated macrophages in vitro, and MMP-12-expressing macrophages were abundant at late, but not early, stages of tuberculosis in murine lungs. Our findings emphasize that alternative activation deprives macrophages of control mechanisms that limit mycobacterial growth in vivo, thus supporting intracellular persistence of M. tuberculosis. PMID:16479545

  20. Antiurolithic activity of Origanum vulgare is mediated through multiple pathways

    PubMed Central

    2011-01-01

    Background Origanum vulgare Linn has traditionally been used in the treatment of urolithiasis. Therefore, we investigated the crude extract of Origanum vulgare for possible antiurolithic effect, to rationalize its medicinal use. Methods The crude aqueous-methanolic extract of Origanum vulgare (Ov.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the in vivo studies, rat model of urolithiasis was used for the study of preventive and curative effect. Results In the in vitro experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm2) crystals. Ov.Cr relaxed high K+ (80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH4Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls. Conclusion These data indicating the antiurolithic activity in Ov.Cr, possibly mediated

  1. How do persons with chronic low back pain speed up and slow down? Trunk-pelvis coordination and lumbar erector spinae activity during gait.

    PubMed

    Lamoth, Claudine J C; Daffertshofer, Andreas; Meijer, Onno G; Beek, Peter J

    2006-02-01

    In healthy walking, the timing between trunk and pelvic rotations, as well as erector spinae (ES) activity varies systematically with walking velocity, whereas a comparable velocity-dependent adaptation of trunk-pelvis coordination is often reduced or absent in persons with low back pain (LBP). Based on the hypothesis that trunk-pelvis coordination is linked to overall gait stability, persons with LBP can be expected to have difficulties in dealing with perturbations. We examined the ability of 12 persons with LBP and 12 controls to adapt trunk and pelvis rotations and ES activity to sudden changes in velocity. 3D angular movements of thoracic, lumbar, and pelvic segments and surface EMG were recorded during treadmill walking at six different velocities, which increased or decreased unexpectedly. Relative phases of segmental rotations were determined and (in-)variant properties of kinematics and ES activity were studied using principal component analysis. Compared to healthy controls, persons with LBP exhibited a reduced ability to adapt trunk-pelvis coordination and ES muscle activity to changes in velocity. Altered coordination and muscular control may reflect an attempt to stabilise the spine and prevent the occurrence of unexpected perturbations. The assessment of gait patterns in terms of coordination may help clinicians to quantify movement impairments and may suggest interventions aimed at facilitating the emergence of desired coordination patterns.

  2. Coordinate activation of human platelet protease-activated receptor-1 and -4 in response to subnanomolar alpha-thrombin.

    PubMed

    Ofosu, Frederick A; Dewar, Lori; Craven, Sharon J; Song, Yingqi; Cedrone, Aisha; Freedman, John; Fenton, John W

    2008-10-01

    We previously demonstrated that human platelets activated with SFLLRN release PAR-1 activation peptide, PAR-1-(1-41), even in the presence of hirudin. This observation suggests that during their activation, platelets generate a protease that activates PAR-1. In this study, PAR-1 and -4 activation peptides were detected 10 s after activation peptides was complete at 10 s. Generation of both PAR-1 and -4 activation peptides in response to 1 nm alpha-thrombin was significantly inhibited by affinity-purified anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, and by the specific PAR-1 antagonist BMS 200261, but not by the PAR-4 antagonist YD3. Effective inhibition of platelet aggregation in response to 1.0 nm alpha-thrombin occurred only in the presence of both anti-PAR span antibodies. We conclude that platelet activation initiated with activation. Inhibiting the activation of either PAR inhibits activation of the other. Both PAR-1 and -4 activation must be inhibited to prevent platelet activation subsequent to thrombin binding to platelets. The more efficient generation of PAR activation peptides by platelets activated with SFLLRN or AYGPKF, compared with alpha-thrombin, indicates that a platelet-derived serine protease that is inactivated by soybean trypsin inhibitor propagates PAR-1 and -4 activation. PMID:18682394

  3. Coordination of spinal locomotor activity in the lamprey: long-distance coupling of spinal oscillators.

    PubMed

    McClellan, A D; Hagevik, A

    1999-05-01

    The extent and strength of long-distance coupling between locomotor networks in the rostral and caudal spinal cord of larval lamprey were examined with in vitro brain/spinal cord preparations, in which spinal locomotor activity was initiated by chemical microstimulation in the brain, as well as with computer modeling. When locomotor activity and short-distance coupling were blocked in the middle spinal cord for at least 40 segments, burst activity in the rostral and caudal spinal cord was still coupled 1:1, indicating that long-distance coupling is extensive. However, in the absence of short-distance coupling, intersegmental phase lags were not constant but decreased significantly with increasing cycle times, suggesting that long-distance coupling maintains a relatively constant delay rather than a constant phase lag between rostral and caudal bursts. In addition, under these conditions, intersegmental phase lags, measured between rostral and caudal burst activity, were significantly less than normal, and the decrease was greater for longer distances between rostral and caudal locomotor networks. The above result could be mimicked by a computer model consisting of pairs of oscillators in the rostral, middle, and caudal spinal cord that were connected by short- and long-distance coupling. With short-distance coupling blocked in the middle spinal cord, strychnine was applied to either the rostral or caudal spinal cord to convert the pattern locally from right-left alternation to synchronous burst activity. Synchronous burst activity in the rostral spinal cord resulted in a reduction in right-left phase values for burst activity in the caudal cord. These results also could be mimicked by the computer model. Strychnine-induced synchronous burst activity in the caudal spinal cord did not appear to alter the right-left phase values of rostral burst activity. Taken together, the experimental and modeling results suggest that the descending and ascending components of long

  4. Multiple biological activities of human recombinant interleukin 1.

    PubMed Central

    Dinarello, C A; Cannon, J G; Mier, J W; Bernheim, H A; LoPreste, G; Lynn, D L; Love, R N; Webb, A C; Auron, P E; Reuben, R C

    1986-01-01

    Complementary DNA coding for human monocyte interleukin 1 (IL-1), pI 7 form, was expressed in Escherichia coli. During purification, IL-1 activity on murine T cells was associated with the recombinant protein. Homogeneous human recombinant IL-1 (hrIL-1) was tested in several assays to demonstrate the immunological and inflammatory properties attributed to this molecule. hrIL-1 induced proliferative responses in a cloned murine T cell in the presence of suboptimal concentrations of mitogen, whereas no effect was observed with hrIL-1 alone. At concentrations of 0.05 ng/ml, hrIL-1 doubled the response to mitogen (5 X 10(6) half maximal units/mg). Human peripheral blood T cells depleted of adherent cells underwent a blastogenic response and released interleukin 2 in the presence of hrIL-1 and mitogen. hrIL-1 was a potent inflammatory agent by its ability to induce human dermal fibroblast prostaglandin E2 production in vitro and to produce monophasic (endogenous pyrogen) fever when injected into rabbits or endotoxin-resistant mice. These studies establish that the dominant pI 7 form of recombinant human IL-1 possesses immunological and inflammatory properties and acts on the central nervous system to produce fever. Images PMID:3519678

  5. Between molecules and experience: role of early patterns of coordinated activity for the development of cortical maps and sensory abilities.

    PubMed

    Hanganu-Opatz, Ileana L

    2010-09-01

    Sensory systems processing information from the environment rely on precisely formed and refined neuronal networks that build maps of sensory receptor epithelia at different subcortical and cortical levels. These sensory maps share similar principles of function and emerge according to developmental processes common in visual, somatosensory and auditory systems. Whereas molecular cues set the coarse organization of cortico-subcortical topography, its refinement is known to succeed under the influence of experience-dependent electrical activity during critical periods. However, coordinated patterns of activity synchronize the cortico-subcortical networks long before the meaningful impact of environmental inputs on sensory maps. Recent studies elucidated the cellular and network mechanisms underlying the generation of these early patterns of activity and highlighted their similarities across species. Moreover, the experience-independent activity appears to act as a functional template for the maturation of sensory networks and cortico-subcortical maps. A major goal for future research will be to analyze how this early activity interacts with the molecular cues and to determine whether it is permissive or rather supporting for the establishment of sensory topography. PMID:20381527

  6. 14-3-3ζ Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells

    PubMed Central

    Li, Wenliang; Xiong, Qian; Yang, Mingkun; Zheng, Peng; Li, Chongyang; Pei, Jianfeng; Ge, Feng

    2012-01-01

    The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3ζ, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3ζ interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3ζ interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3ζ interaction and mutation of Ser727 to Alanine abolished 14-3-3ζ/Stat3 association. Inhibition of 14-3-3ζ protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3ζ is involved in the regulation of protein kinase C (PKC) activity and 14-3-3ζ binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3ζ serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells. PMID:22279540

  7. Co-activation Probability Estimation (CoPE): An approach for modeling functional co-activation architecture based on neuroimaging coordinates.

    PubMed

    Chu, Congying; Fan, Lingzhong; Eickhoff, Claudia R; Liu, Yong; Yang, Yong; Eickhoff, Simon B; Jiang, Tianzi

    2015-08-15

    Recent progress in functional neuroimaging has prompted studies of brain activation during various cognitive tasks. Coordinate-based meta-analysis has been utilized to discover the brain regions that are consistently activated across experiments. However, within-experiment co-activation relationships, which can reflect the underlying functional relationships between different brain regions, have not been widely studied. In particular, voxel-wise co-activation, which may be able to provide a detailed configuration of the co-activation network, still needs to be modeled. To estimate the voxel-wise co-activation pattern and deduce the co-activation network, a Co-activation Probability Estimation (CoPE) method was proposed to model within-experiment activations for the purpose of defining the co-activations. A permutation test was adopted as a significance test. Moreover, the co-activations were automatically separated into local and long-range ones, based on distance. The two types of co-activations describe distinct features: the first reflects convergent activations; the second represents co-activations between different brain regions. The validation of CoPE was based on five simulation tests and one real dataset derived from studies of working memory. Both the simulated and the real data demonstrated that CoPE was not only able to find local convergence but also significant long-range co-activation. In particular, CoPE was able to identify a 'core' co-activation network in the working memory dataset. As a data-driven method, the CoPE method can be used to mine underlying co-activation relationships across experiments in future studies.

  8. Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells

    SciTech Connect

    Hirose, Yoshikazu; Itoh, Tohru; Miyajima, Atsushi

    2009-09-10

    Hedgehog (Hh) signaling plays crucial roles in development and homeostasis of various organs. In the adult liver, it regulates proliferation and/or viability of several types of cells, particularly under injured conditions, and is also implicated in stem/progenitor cell maintenance. However, the role of this signaling pathway during the normal developmental process of the liver remains elusive. Although Sonic hedgehog (Shh) is expressed in the ventral foregut endoderm from which the liver derives, the expression disappears at the onset of the liver bud formation, and its possible recurrence at the later stages has not been investigated. Here we analyzed the activation and functional relevance of Hh signaling during the mouse fetal liver development. At E11.5, Shh and an activation marker gene for Hh signaling, Gli1, were expressed in Dlk{sup +} hepatoblasts, the fetal liver progenitor cells, and the expression was rapidly decreased thereafter as the development proceeded. In the culture of Dlk{sup +} hepatoblasts isolated from the E11.5 liver, activation of Hh signaling stimulated their proliferation and this effect was cancelled by a chemical Hh signaling inhibitor, cyclopamine. In contrast, hepatocyte differentiation of Dlk{sup +} hepatoblasts in vitro as manifested by the marker gene expression and acquisition of ammonia clearance activity was significantly inhibited by forced activation of Hh signaling. Taken together, these results demonstrate the temporally restricted manner of Hh signal activation and its role in promoting the hepatoblast proliferation, and further suggest that the pathway needs to be shut off for the subsequent hepatic differentiation of hepatoblasts to proceed normally.

  9. Systematic assessment of coordinated activity cliffs formed by kinase inhibitors and detailed characterization of activity cliff clusters and associated SAR information.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2015-01-27

    From currently available kinase inhibitors and their activity data, clusters of coordinated activity cliffs were systematically derived and subjected to cluster index and index map analysis. Type I-like inhibitors with well-defined IC50 measurements were found to provide a large knowledge base of activity cliff clusters for 266 targets from nine kinase groups. On the basis of index map analysis, these clusters were systematically organized according to structural similarity of inhibitors and activity cliff diversity and prioritized for structure-activity relationship (SAR) analysis. From prioritized clusters, interpretable SAR information can be extracted. It is also shown that activity cliff clusters formed by ATP site-directed inhibitors often represent local SAR environments of rather different complexity and interpretability. In addition, activity cliff clusters including promiscuous kinase inhibitors have been determined. Only a small subset of inhibitors was found to change activity cliff roles in different clusters. The activity cliff clusters described herein and their index map organization substantially enrich SAR information associated with kinase inhibitors in compound subsets of limited size. The cluster and index map information is made available upon request to provide opportunities for further SAR exploration. On the basis of our analysis and the data provided, activity cliff clusters and corresponding inhibitor series for kinase targets of interest can be readily selected.

  10. Multiple monoaminergic modulation of posturo-locomotor network activity in the newborn rat spinal cord

    PubMed Central

    Beliez, Lauriane; Barrière, Gregory; Bertrand, Sandrine S.; Cazalets, Jean-René

    2014-01-01

    Studies devoted to understanding locomotor control have mainly addressed the functioning of the neural circuits controlling leg movements and relatively little is known of the operation of networks that activate trunk muscles in coordination with limb movements. The aim of the present work was (1) to identify the exogenous neurotransmitter cocktail that most strongly activates postural thoracic circuitry; (2) to investigate how the biogenic amines serotonin (5-HT), dopamine (DA), and noradrenaline (NA) modulate the coordination between limb and axial motor networks. Experiments were carried out on in vitro isolated spinal cord preparations from newborn rats. We recorded from ventral roots to monitor hindlimb locomotor and axial postural network activity. Each combination of the three amines with excitatory amino acids (EAAs) elicited coordinated rhythmic motor activity at all segmental levels with specific characteristics. The variability in cycle period was similar with 5-HT and DA while it was significantly higher with NA. DA elicited motor bursts of smaller amplitude in thoracic segments compared to 5-HT and NA, while both DA and NA elicited motor bursts of higher amplitude than 5-HT in the lumbar and sacral segments. The amines modulated the phase relationships of bursts in various segments with respect to the reference lumbar segment. At the thoracic level there was a phase lag between all recorded segments in the presence of 5-HT, while DA and NA elicited synchronous bursting. At the sacral level, 5-HT and DA induced an intersegmental phase shift while relationships became phase-locked with NA. Various combinations of EAAs with two or even all three amines elicited rhythmic motor output that was more variable than with one amine alone. Our results provide new data on the coordinating processes between spinal cord networks, demonstrating that each amine has a characteristic “signature” regarding its specific effect on intersegmental phase relationships

  11. Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death

    PubMed Central

    Bitomsky, Nadja; Conrad, Elisa; Moritz, Christian; Polonio-Vallon, Tilman; Sombroek, Dirk; Schultheiss, Kathrin; Glas, Carolina; Greiner, Vera; Herbel, Christoph; Mantovani, Fiamma; del Sal, Giannino; Peri, Francesca; Hofmann, Thomas G.

    2013-01-01

    Excessive genome damage activates the apoptosis response. Protein kinase HIPK2 is a key regulator of DNA damage-induced apoptosis. Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. Moreover, HIPK2 autophosphorylation is conserved between human and zebrafish and is important for DNA damage-induced apoptosis in vivo. Mechanistically, autophosphorylation creates a binding signal for the phospho-specific isomerase Pin1. Pin1 links HIPK2 activation to its stabilization by inhibiting HIPK2 polyubiquitination and modulating Siah-1–HIPK2 interaction. Concordantly, Pin1 is required for DNA damage-induced HIPK2 stabilization and p53 Ser46 phosphorylation and is essential for induction of apotosis both in cellulo and in zebrafish. Our results identify an evolutionary conserved mechanism regulating DNA damage-induced apoptosis. PMID:24145406

  12. Metal based isatin-derived sulfonamides: their synthesis, characterization, coordination behavior and biological activity.

    PubMed

    Chohan, Zahid H; Supuran, Claudiu T; Ben Hadda, Taibi; Nasim, Faiz-Ul-Hassan; Khan, Khalid M

    2009-06-01

    Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II), Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure of synthesized compounds and their nature of bonding have been inferred on the basis of their physical (magnetic susceptibility and conductivity measurements), analytical (elemental analyses) and spectral (IR, (1)H NMR and (13)C NMR) properties. An octahedral geometry has been suggested for Co(II), Ni(II) and Zn(II) and square-planar for Cu(II) complexes. In order to assess the antibacterial and antifungal behavior, the ligands and their metal(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis and, for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. In vitro cytotoxic properties of all the compounds were also studied against Artemia salina by brine shrimp bioassay. The results of average antibacterial/antifungal activity showed that zinc(II) complexes were found to be the most active against one or more bacterial/fungal strains as compared to the other metal complexes. PMID:18825557

  13. Topoisomerase inhibition, nucleolytic and electrolytic contribution on DNA binding activity exerted by biological active analogue of coordination compounds.

    PubMed

    Patel, Mohan N; Bhatt, Bhupesh S; Dosi, Promise A

    2012-04-01

    The neutral mononuclear copper complexes with the quinolone antibacterial drug ciprofloxacin and bipyridine derivatives have been synthesized and characterized. Complexes were screened for their antibacterial activity against three Gram((-)) and two Gram((+)) bacteria, and study suggests inhibition of gyrase activity by metal complexes as the possible mechanism. The nucleolytic activity of adducts was carried out on double stranded pUC19 DNA using gel electrophoresis in the presence of radical scavenging agents that suggest hydrolytic cleavage mechanism for plasmid DNA.

  14. Electromyographic Activity of Hand Muscles in a Motor Coordination Game: Effect of Incentive Scheme and Its Relation with Social Capital

    PubMed Central

    Censolo, Roberto; Craighero, Laila; Ponti, Giovanni; Rizzo, Leonzio; Canto, Rosario; Fadiga, Luciano

    2011-01-01

    Background A vast body of social and cognitive psychology studies in humans reports evidence that external rewards, typically monetary ones, undermine intrinsic motivation. These findings challenge the standard selfish-rationality assumption at the core of economic reasoning. In the present work we aimed at investigating whether the different modulation of a given monetary reward automatically and unconsciously affects effort and performance of participants involved in a game devoid of visual and verbal interaction and without any perspective-taking activity. Methodology/Principal Findings Twelve pairs of participants were submitted to a simple motor coordination game while recording the electromyographic activity of First Dorsal Interosseus (FDI), the muscle mainly involved in the task. EMG data show a clear effect of alternative rewards strategies on subjects' motor behavior. Moreover, participants' stock of relevant past social experiences, measured by a specifically designed questionnaire, was significantly correlated with EMG activity, showing that only low social capital subjects responded to monetary incentives consistently with a standard rationality prediction. Conclusions/Significance Our findings show that the effect of extrinsic motivations on performance may arise outside social contexts involving complex cognitive processes due to conscious perspective-taking activity. More importantly, the peculiar performance of low social capital individuals, in agreement with standard economic reasoning, adds to the knowledge of the circumstances that makes the crowding out/in of intrinsic motivation likely to occur. This may help in improving the prediction and accuracy of economic models and reconcile this puzzling effect of external incentives with economic theory. PMID:21464986

  15. Coordinating Government Funding of File System and I/O Research through the High End Computing University Research Activity

    SciTech Connect

    Grider, Gary; Nunez, James; Bent, John; Ross, Rob; Ward, Lee; Poole, Steve; Felix, Evan J.; Salmon, Ellen; Bancroft, Marti

    2009-01-01

    In 2003, the High End Computing Revitalization Task Force designated file systems and I/O as an area in need of national focus. The purpose of the High End Computing Interagency Working Group (HECIWG) is to coordinate government spending on File Systems and 1I0 (FSIO) R&D by all the government agencies that are involved in High End Computing. The HECIWG tasked a smaller advisory group to list, categorize, and prioritize HEC VO and File Systems R&D needs. In 2005, leaders in FSIO from academia, industry and government agencies collaborated to Jist and prioritize areas of research in HEC FSIO. This led to a very successful High End Computing University Research Activity (HECURA) call from NSF in 2006 and has prompted a new HECURA call from NSF in 2009. This paper serves as both a review of the 2008 HEC FSIO identified research gaps as well as a preview of this forthcoming HECURA call.

  16. Coordinated Observations of the Active Binary σ 2 CrB with Chandra, EUVE, and the VLA

    NASA Astrophysics Data System (ADS)

    Osten, R. A.; Brown, A.; Ayres, T. R.; Krishnamurthi, A.; Linsky, J. L.

    2000-10-01

    We report on coordinated observations of the short-period active binary σ 2 CrB (F6V + G0V, P orb=1.14 d) taken with the Chandra X-ray Observatory, the Extreme Ultraviolet Explorer, and the Very Large Array. EUVE observations span more than 7 orbital periods of the system. Centered in the middle of the nine day EUVE observation is a Chandra ACIS-S+HETGS grating observation lasting 85 ks and an overlapping 12 hour multifrequency VLA observation. We discuss the coronal variability, present high-resolution X-ray spectra and preliminary analysis including the search for flares, and tie the thermal high temperature emission together with nonthermal coronal emission. RAO acknowledges funding from a NASA GSRP fellowship, grant NGT5-50241. AB and TRA acknowledge funding from NASA grant NAG5-3226, and JLL acknowledges support from NASA through grants S-56500-D and H-04630D.

  17. HYSCORE Analysis of the Effects of Substrates on Coordination of Water to the Active Site Iron in Tyrosine Hydroxylase.

    PubMed

    McCracken, John; Eser, Bekir E; Mannikko, Donald; Krzyaniak, Matthew D; Fitzpatrick, Paul F

    2015-06-23

    Tyrosine hydroxylase is a mononuclear non-heme iron monooxygenase found in the central nervous system that catalyzes the hydroxylation of tyrosine to yield L-3,4-dihydroxyphenylalanine, the rate-limiting step in the biosynthesis of catecholamine neurotransmitters. Catalysis requires the binding of tyrosine, a tetrahydropterin, and O₂ at an active site that consists of a ferrous ion coordinated facially by the side chains of two histidines and a glutamate. We used nitric oxide as a surrogate for O₂ to poise the active site iron in an S = ³/₂ {FeNO}⁷ form that is amenable to electron paramagnetic resonance (EPR) spectroscopy. The pulsed EPR method of hyperfine sublevel correlation (HYSCORE) spectroscopy was then used to probe the ligands at the remaining labile coordination sites on iron. For the complex formed by the addition of tyrosine and nitric oxide, TyrH/NO/Tyr, orientation-selective HYSCORE studies provided evidence of the coordination of one H₂O molecule characterized by proton isotropic hyperfine couplings (A(iso) = 0.0 ± 0.3 MHz) and dipolar couplings (T = 4.4 and 4.5 ± 0.2 MHz). These data show complex HYSCORE cross peak contours that required the addition of a third coupled proton, characterized by an A(iso) of 2.0 MHz and a T of 3.8 MHz, to the analysis. This proton hyperfine coupling differed from those measured previously for H₂O bound to {FeNO}⁷ model complexes and was assigned to a hydroxide ligand. For the complex formed by the addition of tyrosine, 6-methyltetrahydropterin, and NO, TyrH/NO/Tyr/6-MPH₄, the HYSCORE cross peaks attributed to H₂O and OH⁻ for the TyrH/NO/Tyr complex were replaced by a cross peak due to a single proton characterized by an A(iso) of 0.0 MHz and a dipolar coupling (T = 3.8 MHz). This interaction was assigned to the N₅ proton of the reduced pterin.

  18. Progress and status of the IAEA coordinated research project: production of Mo-99 using LEU fission or neutron activation

    SciTech Connect

    Goldman, Ira N.; Adelfang, Pablo E-mail: P.Adelfang@iaea.org; Ramamoorthy, Natesan

    2008-07-15

    Since late 2004, the IAEA has developed and implemented a Coordinated Research Project (CRP) to assist countries interested in initiating indigenous, small-scale production of Mo-99 to meet local nuclear medicine requirements. The objective of the CRP is to provide interested countries with access to non-proprietary technologies and methods to produce Mo-99 using LEU foil or LEU mini-plate targets, or for the utilization of n,gamma neutron activation, e.g. through the use of gel generators. The project has made further progress since the RERTR 2006 meeting, with a Technical Workshop on Operational Aspects of Mo99 Production held 28-30 November 2006 in Vienna and the Second Research Coordination Meeting held in Bucharest, Romania 16-20 April 2007. The paper describes activities carried out as noted above, and as well as the provision of LEU foils to a number of participants, and the progress by a number of groups in preparing for LEU target assembly and disassembly, irradiation, chemical processing, and waste management. The participants' progress in particular on thermal hydraulics computations required for using LEU targets is notable, as also the progress in gel generator plant operations in India and Kazakhstan. Poland has joined as a new research agreement holder and an application by Egypt to be a contract holder is undergoing internal review in the IAEA and is expected to be approved. The IAEA has also participated in several open meetings of the U.S. National Academy of Sciences Study on Producing Medical Radioisotopes without HEU, which will also be discussed in the paper. (author)

  19. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  20. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  1. Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

    2013-01-01

    Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

  2. An Architecture for Controlling Multiple Robots

    NASA Technical Reports Server (NTRS)

    Aghazarian, Hrand; Pirjanian, Paolo; Schenker, Paul; Huntsberger, Terrance

    2004-01-01

    The Control Architecture for Multirobot Outpost (CAMPOUT) is a distributed-control architecture for coordinating the activities of multiple robots. In the CAMPOUT, multiple-agent activities and sensor-based controls are derived as group compositions and involve coordination of more basic controllers denoted, for present purposes, as behaviors. The CAMPOUT provides basic mechanistic concepts for representation and execution of distributed group activities. One considers a network of nodes that comprise behaviors (self-contained controllers) augmented with hyper-links, which are used to exchange information between the nodes to achieve coordinated activities. Group behavior is guided by a scripted plan, which encodes a conditional sequence of single-agent activities. Thus, higher-level functionality is composed by coordination of more basic behaviors under the downward task decomposition of a multi-agent planner

  3. Metallo-beta-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily.

    PubMed

    Bebrone, Carine

    2007-12-15

    One strategy employed by bacterial strains to resist beta-lactam antibiotics is the expression of metallo-beta-lactamases requiring Zn(2+) for activity. In the last few years, many new zinc beta-lactamases have been described and several pathogens are now known to synthesize members of this class. Metallo-beta-lactamases are especially worrisome due to: (1) their broad activity profiles that encompass most beta-lactam antibiotics, including the carbapenems; (2) potential for horizontal transference; and (3) the absence of clinically useful inhibitors. On the basis of the known sequences, three different lineages, identified as subclasses B1, B2, and B3 have been characterized. The three-dimensional structure of at least one metallo-beta-lactamase of each subclass has been solved. These very similar 3D structures are characterized by the presence of an alphabetabetaalpha-fold. In addition to metallo-beta-lactamases which cleave the amide bond of the beta-lactam ring, the metallo-beta-lactamase superfamily includes enzymes which hydrolyze thiol-ester, phosphodiester and sulfuric ester bonds as well as oxydoreductases. Most of the 6000 members of this superfamily share five conserved motifs, the most characteristic being the His116-X-His118-X-Asp120-His121 signature. They all exhibit an alphabetabetaalpha-fold, similar to that found in the structure of zinc beta-lactamases. Many members of this superfamily are involved in mRNA maturation and DNA reparation. This fact suggests the hypothesis that metallo-beta-lactamases may be the result of divergent evolution starting from an ancestral protein which did not have a beta-lactamase activity.

  4. Coordinated Observations of X-ray and High-resolution EUV Active Region Dynamics

    NASA Technical Reports Server (NTRS)

    Savage, Sabrina

    2013-01-01

    The recently-launched High-resolution Coronal imager (Hi-C) sounding rocket provided the highest resolution images of coronal loops and other small-scale structures in the 193 Angstrom passband to date. With just 5 minutes of observations, the instrument recorded a variety of dynamic coronal events -- including even a small B-class flare. We will present our results comparing these extreme-ultraviolet (EUV) observations with X-ray imaging from Hinode/XRT as well as EUV AIA data to identify sources of hot plasma rooted in the photosphere and track their affect on the overall topology and dynamics of the active region.

  5. Coordinated Observations of X-ray and High-Resolution EUV Active Region Dynamics

    NASA Technical Reports Server (NTRS)

    Savage, Sabrina; Cirtain, Jonathan; Winebarger, Amy; Kobayashi, Ken; Golub, Leon; Korreck, Kelly

    2013-01-01

    The recently-launched High-resolution Coronal imager (Hi-C) sounding rocket provided the highest resolution images of coronal loops and other small-scale structures in the 193 Angstrom passband to date. With just 5 minutes of observations, the instrument recorded a variety of dynamic coronal events -- including even a small B-class flare. We will present our results comparing these extreme-ultraviolet (EUV) observations with X-ray imaging from Hinode/XRT as well as EUV AIA data to identify sources of hot plasma rooted in the photosphere and track their affect on the overall topology and dynamics of the active region.

  6. Redox-active and DNA-binding coordination complexes of clotrimazole.

    PubMed

    Betanzos-Lara, Soledad; Chmel, Nikola P; Zimmerman, Matthew T; Barrón-Sosa, Lidia R; Garino, Claudio; Salassa, Luca; Rodger, Alison; Brumaghim, Julia L; Gracia-Mora, Isabel; Barba-Behrens, Norah

    2015-02-28

    DNA interactions of anticancer mononuclear Cu(2+), Co(2+), Zn(2+), and Ni(2+) complexes with the biologically active ligand clotrimazole (clotri) are reported. To fully characterize DNA binding modes for these complexes of the formulae [M(clotri)2Cl2]·nH2O (1-4), [M(clotri)2Br2]·nH2O (5,6), [M(clotri)3NO3]NO3·nH2O (9), and [M(clotri)3(NO3)2] (10), circular dichroism (CD) and linear dichroism (LD) spectroscopy, UV melting experiments, atomic force microscopy (AFM) and ethidium bromide (EtBr) displacement methods were used. Results indicate mixed electrostatic interactions, possibly through groove binding, that result in accretion and coiling of DNA. Electrochemical studies indicate that the Cu(2+) complex 9 readily reduces to the reactive-oxygen-species-generating Cu(+), which oxidatively damages DNA. There is a subtle correlation between log P values, calculated electrostatic potentials, and cytotoxicity of the complexes. The extent of cell-nucleus DNA-metal adduct formation in the HeLa cervix-uterine carcinoma cell line does not necessarily correlate with cytotoxicity, indicating that the nature of DNA lesions may be crucial to activity. PMID:25561277

  7. A Coordinated Study of Flares and Active Regions on the by Draconis-Type Star CC Eridani

    NASA Astrophysics Data System (ADS)

    Linsky, Jeffrey L.

    We propose to observe the 1.56 day period spectroscopic binary CC Eri (K7Ve + dM?) continuously over its complete orbital period in order (1) to measure the ultraviolet emission from it's active regions and it's quiescent atmosphere separately and (2) to study flares that likely will occur during the observing run. CC Eri is the second brightest member of the BY Draconis class of spotted cool dwarfs, it has the shortest known orbital and rotational period, and it has the fastest rotational velocity of the BY Dra class. For these reasons it is likely a very active member and probably has one of the brightest ultraviolet emission line spectrum of its class. Since only one IUE spectrum has so far been obtained of this important object, we propose to begin a detailed study of its ultraviolet emission properties leading to a high-dispersion SWP observation next year. We will obtain a continuous series of SWP-LO and LWP-LO spectra over the full orbital (= rotational period) in order to identify bright active regions (from the rotational modulation of emission line fluxes) and to correlate the location of these active regions with dark starspots, whose positions will be determined from contemporaneous optical photometry and spectroscopy. We also will study the time behavior of flares in different spectral lines and with coordinated optical photometry and VLA radio observations. Flares with U-magnitude enhancements greater than I magnitude are known to occur on average once every 12 hours. We plan to model the quiescent, active, and flaring atmospheres separately using emission measure diagnostics. CC Eri is an excellent candidate for this study, because it usually has a large amplitude photometric variation indicating an asymmetric distribution of spots (and thus active regions) across its surface, while it's flares are few but energetic. IUE is particularly well suited for such modulation studies.

  8. CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.

    PubMed

    Aregger, Michael; Kaskar, Aneesa; Varshney, Dhaval; Fernandez-Sanchez, Maria Elena; Inesta-Vaquera, Francisco A; Weidlich, Simone; Cowling, Victoria H

    2016-03-01

    The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate. PMID:26942677

  9. CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription

    PubMed Central

    Aregger, Michael; Kaskar, Aneesa; Varshney, Dhaval; Fernandez-Sanchez, Maria Elena; Inesta-Vaquera, Francisco A.; Weidlich, Simone; Cowling, Victoria H.

    2016-01-01

    Summary The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate. PMID:26942677

  10. Coordination and activation of Al-H and Ga-H bonds.

    PubMed

    Abdalla, Joseph A B; Riddlestone, Ian M; Turner, Joshua; Kaufman, Paul A; Tirfoin, Remi; Phillips, Nicholas; Aldridge, Simon

    2014-12-22

    The modes of interaction of donor-stabilized Group 13 hydrides (E=Al, Ga) were investigated towards 14- and 16-electron transition-metal fragments. More electron-rich N-heterocyclic carbene-stabilized alanes/gallanes of the type NHC⋅EH3 (E=Al or Ga) exclusively generate κ(2) complexes of the type [M(CO)4 (κ(2)-H3 E⋅NHC)] with [M(CO)4 (COD)] (M=Cr, Mo), including the first κ(2) σ-gallane complexes. β-Diketiminato ('nacnac')-stabilized systems, {HC(MeCNDipp)2 }EH2 , show more diverse reactivity towards Group 6 carbonyl reagents. For {HC(MeCNDipp)2 }AlH2, both κ(1) and κ(2) complexes were isolated, while [Cr(CO)4 (κ(2)-H2 Ga{(NDippCMe)2 CH})] is the only simple κ(2) adduct of the nacnac-stabilized gallane which can be trapped, albeit as a co-crystallite with the (dehydrogenated) gallylene system [Cr(CO)5 (Ga{(NDippCMe)2 CH})]. Reaction of [Co2 (CO)8] with {HC(MeCDippN)2 }AlH2 generates [(OC)3 Co(μ-H)2 Al{(NdippCme)2 CH}][Co(CO)4] (12), which while retaining direct AlH interactions, features a hitherto unprecedented degree of bond activation in a σ-alane complex. PMID:25358970

  11. Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling

    PubMed Central

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Kim, Hyo Jeong; Ko, Myoung Seok; Seol, Wongi; Joe, Yeonsoo; Chung, Hun Taeg; Lee, Byung Ju; Moon, Chang Hoon; Cho, Wha Ja; Park, Jeong Woo

    2016-01-01

    The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling. DRG2 was associated with phosphatidylinositol 3-phosphate–containing endosomes. It colocalized and interacted with EEA1 and Rab5 on endosomes in a phosphatidylinositol 3-kinase–dependent manner. DRG2 depletion did not affect Tfn uptake and recruitment of RabGAP5 and Rac1 to Rab5 endosomes. However, it resulted in impairment of interaction between Rab5 and RabGAP5, Rab5 deactivation on endosomes, and Tfn recycling. Ectopic expression of shRNA-resistant DRG2 rescued Tfn recycling in DRG2-depleted cells. Our results demonstrate that DRG2 is an endosomal protein and a key regulator of Rab5 deactivation and Tfn recycling. PMID:26582392

  12. Coordination behavior and antifungicidal, antibacterial, and antifertility activities of dioxomolybdenum(VI) complexes of biologically active heterocyclic benzothiazolines.

    PubMed

    Kanoongo, N; Singh, R V; Tandon, J P; Goyal, R B

    1990-01-01

    Synthesis, characterization, and structural aspects of a new class of dioxomolybdenum(VI) complexes with biologically active benzothiazolines, 2-(2-pyridyl) benzothiazoline, 2-(2-thienyl) benzothiazoline, 2-(2-furyl) benzothiazoline, 2-(3-indolyl) benzothiazoline, glyoxal benzothiazoline, biacetylbenzothiazoline, benzil benzothiazoline, and terphthaldehyde benzothiazoline have been described. The newly synthesized complexes, [MoO2(Bzt)2] and [MoO2(Bzt')] (where BztH and Bzt'H2 represent benzothazoline molecules) have been characterized by elemental analysis, conductance measurements, molecular weight determinations, and magnetic studies. Based on IR, 1H NMR, 13C NMR, and electronic spectral studies, distorted octahedral geometry with cis-MoO2 group has been indicated for the resulting complexes. Two benzothiazolines and their corresponding metal complexes were screened for their antifungicidal and antibacterial activity on several fungi and bacteria and found to be quite active in this respect. In addition, antifertility activity of representative ligands and their molybdenum complexes was also evaluated and discussed in male mice.

  13. Variations in CT determination of target volume with active breath co-ordinate in radiotherapy for post-operative gastric cancer

    PubMed Central

    Li, Gui-Chao; Ma, Xue-Jun; Yu, Xiao-Li; Hu, Wei-Gang; Wang, Jia-Zhou; Li, Qi-Wen; Liang, Li-Ping; Shen, Li-Jun; Zhang, Hui; Fan, Ming

    2016-01-01

    Objective: To investigate interobserver and inter-CT variations in using the active breath co-ordinate technique in the determination of clinical tumour volume (CTV) and normal organs in post-operative gastric cancer radiotherapy. Methods: Ten gastric cancer patients were enrolled in our study, and four radiation oncologists independently determined the CTVs and organs at risk based on the CT simulation data. To determine interobserver and inter-CT variation, we evaluated the maximum dimensions, derived volume and distance between the centres of mass (CMs) of the CTVs. We assessed the reliability in CTV determination among the observers by conformity index (CI). Results: The average volumes ± standard deviation (cm3) of the CTV, liver, left kidney and right kidney were 674 ± 138 (range, 332–969), 1000 ± 138 (range, 714–1320), 149 ± 13 (range, 104–183) and 141 ± 21 (range, 110–186) cm3, respectively. The average inter-CT distances between the CMs of the CTV, liver, left kidney and right kidney were 0.40, 0.56, 0.65 and 0.6 cm, respectively; the interobserver values were 0.98, 0.53, 0.16 and 0.15 cm, respectively. Conclusions: In the volume size of CTV for post-operative gastric cancer, there were significant variations among multiple observers, whereas there was no variation between different CTs. The slices in which variations more likely occur were the slices of the lower verge of the hilum of the spleen and porta hepatis, then the paraoesophageal lymph nodes region and abdominal aorta, and the inferior vena cava, and the variation in the craniocaudal orientation from the interobserver was more predominant than that from inter-CT. Advances in knowledge: First, this is the first study to evaluate the interobserver and inter-CT variations in the determination of the CTV and normal organs in gastric cancer with the use of the active breath co-ordinate technique. Second, we analysed the region where variations most likely occur

  14. Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

    PubMed Central

    Abou-Hussein, Azza A.; Linert, Wolfgang

    2014-01-01

    Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet–visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms. PMID:24070648

  15. A Laboratory of Extremophiles: Iceland Coordination Action for Research Activities on Life in Extreme Environments (CAREX) Field Campaign.

    PubMed

    Marteinsson, Viggó; Vaishampayan, Parag; Kviderova, Jana; Mapelli, Francesca; Medori, Mauro; Calfapietra, Carlo; Aguilera, Angeles; Hamisch, Domenica; Reynisson, Eyjólfur; Magnússon, Sveinn; Marasco, Ramona; Borin, Sara; Calzada, Abigail; Souza-Egipsy, Virginia; González-Toril, Elena; Amils, Ricardo; Elster, Josef; Hänsch, Robert

    2013-02-25

    Existence of life in extreme environments has been known for a long time, and their habitants have been investigated by different scientific disciplines for decades. However, reports of multidisciplinary research are uncommon. In this paper, we report an interdisciplinary three-day field campaign conducted in the framework of the Coordination Action for Research Activities on Life in Extreme Environments (CAREX) FP7EU program, with participation of experts in the fields of life and earth sciences. In situ experiments and sampling were performed in a 20 m long hot springs system of different temperature (57 °C to 100 °C) and pH (2 to 4). Abiotic factors were measured to study their influence on the diversity. The CO2 and H2S concentration varied at different sampling locations in the system, but the SO2 remained the same. Four biofilms, mainly composed by four different algae and phototrophic protists, showed differences in photosynthetic activity. Varying temperature of the sampling location affects chlorophyll fluorescence, not only in the microbial mats, but plants (Juncus), indicating selective adaptation to the environmental conditions. Quantitative polymerase chain reaction (PCR), DNA microarray and denaturing gradient gel electrophoresis (DGGE)-based analysis in laboratory showed the presence of a diverse microbial population. Even a short duration (30 h) deployment of a micro colonizer in this hot spring system led to colonization of microorganisms based on ribosomal intergenic spacer (RISA) analysis. Polyphasic analysis of this hot spring system was possible due to the involvement of multidisciplinary approaches.

  16. Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

    NASA Astrophysics Data System (ADS)

    Abou-Hussein, Azza A.; Linert, Wolfgang

    2014-01-01

    Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet-visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms.

  17. Rhythmic motor activity and interlimb co-ordination in the developing pouch young of a wallaby (Macropus eugenii).

    PubMed Central

    Ho, S M

    1997-01-01

    1. The forelimb motor behaviour of developing wallaby was studied. A clock-like alternating movement was reactivated whenever the animal was removed from the pouch. 2. Forelimb stepping frequency increased during the first 3 weeks of development, while the phase relationship remained constant. Forelimb activity could be affected by altering the afferent feedback from the contralateral limb, or an increase in ambient temperature. 3. In vitro experiments were performed using an isolated brainstem-spinal cord preparation from animals up to 6 weeks postnatal. Fictive locomotor activity could be evoked by electrical stimulation or bath-applied NMDA (< 10 microM). 4. Bath-applied strychnine (10-25 microM) and bicuculline (10-50 microM) disrupted the phase relationship between motor pools, while rhythmic motor discharge remained in the absence of these inhibitory pathways. 5. The present findings indicate that the pattern generator that underlies the robust forelimb movement during the first journey to the pouch is retained for different motor functions during in-pouch development. The neural network that underlies such behaviour can be divided into two major components, a rhythm generator within each hemicord, and a pattern co-ordinating pathway which involve both glycinergic and GABAergic interneurones. PMID:9218221

  18. Novel nano coordination polymer based synthesis of porous ZnO hexagonal nanodisk for higher gas sorption and photocatalytic activities

    NASA Astrophysics Data System (ADS)

    Rakibuddin, M.; Ananthakrishnan, Rajakumar

    2016-01-01

    Zinc(II)-based nano co-ordination polymers (NCPs) are first prepared at room temperature from three different isomers of dihydroxysalophen (DHS) ligand with Zn(OAc)2·2H2O and 1,4-benzenedicarboxylic acid (BDC) in DMF solvent. Facile calcinations of [Zn (DHS) (BDC)]·nH2O (shortly denoted as Zn(II)-based NCP) at ambient conditions produces porous ZnO hexagonal nanodisks. Moreover, a novel approach has been introduced to observe the effect of ligand of the NCP on the physico-chemical properties of the as-synthesized ZnO. The porous ZnO nanodisks are characterized by FT-IR, PXRD, TEM, FESEM, EDX and BET analysis, and the results exhibit that they possess different sizes, surface areas and porosities. Nitrogen gas sorption capacity and photocatalytic activities of the as-prepared ZnO nanodisks are also checked, and it is noticed that they differ in these physico-chemical properties due to having different porosities and surface areas. A comparative study is also done with commercially available ZnO; interestingly, the commercial ZnO exhibited lower surface area, gas sorption and photocatalytic activity compared to the ZnO nanodisks. Hence, preparation of the ZnO through the NCP route and tuning their physico-chemical properties would offer new directions in synthesis of various nano metal oxides of unique properties.

  19. Developmental coordination disorder

    MedlinePlus

    Physical causes and other types of learning disabilities must be ruled out before the diagnosis can be confirmed. ... Developmental coordination disorder can lead to: Learning problems ... wanting to participate in physical activities (such as sports)

  20. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma.

    PubMed

    Vatolin, Sergei; Phillips, James G; Jha, Babal K; Govindgari, Shravya; Hu, Jennifer; Grabowski, Dale; Parker, Yvonne; Lindner, Daniel J; Zhong, Fei; Distelhorst, Clark W; Smith, Mitchell R; Cotta, Claudiu; Xu, Yan; Chilakala, Sujatha; Kuang, Rebecca R; Tall, Samantha; Reu, Frederic J

    2016-06-01

    Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow-sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active-site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma. Cancer Res; 76(11); 3340-50. ©2016 AACR. PMID:27197150

  1. Technology coordination

    NASA Technical Reports Server (NTRS)

    Hartman, Steven

    1992-01-01

    Viewgraphs on technology coordination are provided. Topics covered include: technology coordination process to date; goals; how the Office of Aeronautics and Space Technology (OAST) can support the Office of Space Science and Applications (OSSA); how OSSA can support OAST; steps to technology transfer; and recommendations.

  2. An Expanded Theoretical Framework of Care Coordination Across Transitions in Care Settings.

    PubMed

    Radwin, Laurel E; Castonguay, Denise; Keenan, Carolyn B; Hermann, Cherice

    2016-01-01

    For many patients, high-quality, patient-centered, and cost-effective health care requires coordination among multiple clinicians and settings. Ensuring optimal care coordination requires a clear understanding of how clinician activities and continuity during transitions affect patient-centeredness and quality outcomes. This article describes an expanded theoretical framework to better understand care coordination. The framework provides clear articulation of concepts. Examples are provided of ways to measure the concepts.

  3. Block coordination copolymers

    DOEpatents

    Koh, Kyoung Moo; Wong-Foy, Antek G; Matzger, Adam J; Benin, Annabelle I; Willis, Richard R

    2012-11-13

    The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

  4. Block coordination copolymers

    DOEpatents

    Koh, Kyoung Moo; Wong-Foy, Antek G.; Matzger, Adam J.; Benin, Annabelle I.; Willis, Richard R.

    2012-12-04

    The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

  5. Block coordination copolymers

    DOEpatents

    Koh, Kyoung Moo; Wong-Foy, Antek G; Matzger, Adam J; Benin, Annabelle I; Willis, Richard R

    2014-11-11

    The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

  6. 6. Coordination and control.

    PubMed

    2014-05-01

    Any complex operation requires a system for management. In most societies, disaster management is the responsibility of the government. Coordination and control is a system that provides the oversight for all of the disaster management functions. The roles and responsibilities of a coordination and control centre include: (1) planning; (2) maintenance of inventories; (3) activation of the disaster response plan; (4) application of indicators of function; (5) surveillance; (6) information management; (7) coordination of activities of the BSFs; (8) decision-making; (9) priority setting; (10) defining overarching goal and objectives for interventions; (11) applying indicators of effectiveness; (12) applying indicators of benefit and impact; (13) exercising authority; (14) managing resources; (15) initiating actions; (16) preventing influx of unneeded resources; (17) defining progress; (18) providing information; (19) liasing with responding organisations; and (20) providing quality assurance. Coordination and control is impossible without communications. To accomplish coordination and control, three factors must be present: (1) mandate; (2) power and authority; and (3) available resources. Coordination and control is responsible for the evaluation of the effectiveness and benefits/impacts of all interventions. Coordination and control centres (CCCs) are organised hierarchically from the on-scene CCCs (incident command) to local provincial to national CCCs. Currently, no comprehensive regional and international CCCs have been universally endorsed. Systems such as the incident command system, the unified command system, and the hospital incident command system are described as are the humanitarian reform movement and the importance of coordination and control in disaster planning and preparedness.

  7. Inverse estimation of multiple muscle activations from joint moment with muscle synergy extraction.

    PubMed

    Li, Zhan; Guiraud, David; Hayashibe, Mitsuhiro

    2015-01-01

    Human movement is produced resulting from synergetic combinations of multiple muscle contractions. The resultant joint movement can be estimated through the related multiple-muscle activities, which is formulated as the forward problem. Neuroprosthetic applications may benefit from cocontraction of agonist and antagonist muscle pairs to achieve more stable and robust joint movements. It is necessary to estimate the activation of each individual muscle from desired joint torque(s), which is the inverse problem. A synergy-based solution is presented for the inverse estimation of multiple muscle activations from joint movement, focusing on one degree-of-freedom tasks. The approach comprises muscle synergy extraction via the nonnegative matrix factorization algorithm. Cross validation is performed to evaluate the method for prediction accuracy based on experimental data from ten able-bodied subjects. The results demonstrate that the approach succeeds to inversely estimate the multiple muscle activities from the given joint torque sequence. In addition, the other one's averaged synergy ratio was applied for muscle activation estimation with leave-one-out cross-validation manner, which resulted in 9.3% estimation error over all the subjects. The obtained results support the common muscle synergy-based neuroprosthetics control concept.

  8. Poisson Coordinates.

    PubMed

    Li, Xian-Ying; Hu, Shi-Min

    2013-02-01

    Harmonic functions are the critical points of a Dirichlet energy functional, the linear projections of conformal maps. They play an important role in computer graphics, particularly for gradient-domain image processing and shape-preserving geometric computation. We propose Poisson coordinates, a novel transfinite interpolation scheme based on the Poisson integral formula, as a rapid way to estimate a harmonic function on a certain domain with desired boundary values. Poisson coordinates are an extension of the Mean Value coordinates (MVCs) which inherit their linear precision, smoothness, and kernel positivity. We give explicit formulas for Poisson coordinates in both continuous and 2D discrete forms. Superior to MVCs, Poisson coordinates are proved to be pseudoharmonic (i.e., they reproduce harmonic functions on n-dimensional balls). Our experimental results show that Poisson coordinates have lower Dirichlet energies than MVCs on a number of typical 2D domains (particularly convex domains). As well as presenting a formula, our approach provides useful insights for further studies on coordinates-based interpolation and fast estimation of harmonic functions.

  9. Peer Interactions among Children with Profound Intellectual and Multiple Disabilities during Group Activities

    ERIC Educational Resources Information Center

    Nijs, Sara; Penne, Anneleen; Vlaskamp, Carla; Maes, Bea

    2016-01-01

    Background: Children with profound intellectual and multiple disabilities (PIMD) meet other children with PIMD in day care centres or schools. This study explores the peer-directed behaviours of children with PIMD, the peer interaction-influencing behaviour of the direct support workers and the children's positioning. Method: Group activities for…

  10. Sport and Physical Activity in a High Security Spanish Prison: An Ethnographic Study of Multiple Meanings

    ERIC Educational Resources Information Center

    Martos-Garcia, Daniel; Devis-Devis, Jose; Sparkes, Andrew C.

    2009-01-01

    Drawing on data generated by a two-year ethnographic study in a high security Spanish prison, this article explores the multiple meanings given to the social practices of sport and physical activity. We provide details of the following key themes that emerged from the analysis: (a) escaping time; (b) perceived therapeutic benefits; (c) social…

  11. Effects of Multiple Intelligences Activities on Writing Skill Development in an EFL Context

    ERIC Educational Resources Information Center

    Gündüz, Zennure Elgün; Ünal, Ismail Dogan

    2016-01-01

    This study aims at exploring the effects of multiple intelligences activities versus traditional method on English writing development of the sixth grade students in Turkey. A quasi-experimental research method with a pre-test post-test design was applied. The participants were 50 sixth grade students at a state school in Ardahan in Turkey. The…

  12. Omaha Public Schools Multiple Activities Program: An Evaluation, ESEA Title I, September 1972 to August 1973.

    ERIC Educational Resources Information Center

    Texley, Lloyd C.; Dvorak, Ronald S.

    The purposes of the Multiple Activities Program, funded under Title I of the 1965 Elementary Secondary Education Act, were: (1) to supplement the instructional program for educationally disadvantaged children by developing a curriculum and techniques, specifically in reading, which would raise their achievement level commensurate with their…

  13. Extent, Duration, and Content of Day Services' Activities for Persons with Profound Intellectual and Multiple Disabilities

    ERIC Educational Resources Information Center

    Vlaskamp, Carla; Hiemstra, Saskia J.; Wiersma, Linda A.; Zijlstra, Bonne J. H.

    2007-01-01

    In the Netherlands, the Dutch government instituted policies that enable persons with profound intellectual and multiple disabilities (PIMD) to attend day services. Over the past 15 years, surveys have indicated a progressive increase in the number of hours that such adults spend at day activities centers. However, information about how these…

  14. Active Learning and Threshold Concepts in Multiple Testing That Can Further Develop Student Critical Statistical Thinking

    ERIC Educational Resources Information Center

    White, Desley

    2015-01-01

    Two practical activities are described, which aim to support critical thinking about statistics as they concern multiple outcomes testing. Formulae are presented in Microsoft Excel spreadsheets, which are used to calculate the inflation of error associated with the quantity of tests performed. This is followed by a decision-making exercise, where…

  15. A novel one-dimensional manganese(II) coordination polymer containing both dicyanamide and pyrazinamide ligands: Synthesis, spectroscopic investigations, X-ray studies and evaluation of biological activities

    NASA Astrophysics Data System (ADS)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-03-01

    A novel 1D coordination polymer {[Mn(μ1,5-dca)2(PZA)2](PZA)2}n, 1, has been synthesized and characterized by single crystal X-ray crystallography. The coordination mode of dicyanamide (dca) and pyrazinamide (PZA) ligands was inferred by IR spectroscopy. The compound 1 was evaluated for in vitro antimycobacterial and antitumor activities. It demonstrated better in vitro activity against Mycobacterium tuberculosis than pyrazinamide and its MIC value was determined. Complex 1 was also screened for its in vitro antitumor activity towards LM3 and LP07 murine cancer cell lines. In addition, the antibacterial activity of complex 1 has been tested against Gram(+) and Gram(-) bacteria and it has shown promising broad range anti-bacterial activity.

  16. Innovative Ideas for Coordinating International Space Activities: International Center for Space Medicine, International Space Authority, and other Global Youth Space Initiatives

    NASA Astrophysics Data System (ADS)

    Marshall, W.

    2002-01-01

    The Space Generation Forum SGF, at UNISPACE-III, as one of its ten formal recommendations to the United Nations in 1999, put forward the suggestion that the an international space authority should be created. Other recommendations were the establishment of an International Center for Space Medicine, creation of a global space exploration and development program, establishment of a global space (Nobel) prize, and a global space library. These projects are being further developed at the Space Generation Summit (SGS), an event at World Space Congress (WSC) which shall unite international students and young professionals to develop a youth vision and strategy for the peaceful uses of space. SGS, endorsed by the United Nations, will take place from October 11- 13th, during which the 200 delegates will discuss ongoing youth space activities, particularly those stemming from the UNISPACE-III/SGF and taken forward by the Space Generation Advisory Council. Delegates will address a variety of topics with the goal of devising new recommendations according to the theme, 'Accelerating Our Pace in Space'. The material presented here and in other technical sessions throughout WSC includes the findings of these discussions. In this paper, we present the International Space Authority idea together with recommendations on how that might be taken forward. The purpose of such an organization would be to allow: 1. Oversight and enforcement for the balanced regulation of multiple interests in space 2. Access for all peoples to the material benefits and knowledge and understanding enabled by the exploration and 3. Pooling of national and industry resources for the creation of space infrastructure, missions and enterprises for Operating principles: 1. The ISA regulatory regime would encourage commercialization and the harnessing of competitive market 2. Consistent with its charter to ensure access to all peoples, all UN member states and appropriate NGOs would 3. Close coordination with

  17. Hybrid coordination-network-engineering for bridging cascaded channels to activate long persistent phosphorescence in the second biological window

    NASA Astrophysics Data System (ADS)

    Qin, Xixi; Li, Yang; Zhang, Ruili; Ren, Jinjun; Gecevicius, Mindaugas; Wu, Yiling; Sharafudeen, Kaniyarakkal; Dong, Guoping; Zhou, Shifeng; Ma, Zhijun; Qiu, Jianrong

    2016-02-01

    We present a novel “Top-down” strategy to design the long phosphorescent phosphors in the second biological transparency window via energy transfer. Inherence in this approach to material design involves an ingenious engineering for hybridizing the coordination networks of hosts, tailoring the topochemical configuration of dopants, and bridging a cascaded tunnel for transferring the persistent energy from traps, to sensitizers and then to acceptors. Another significance of this endeavour is to highlight a rational scheme for functionally important hosts and dopants, Cr/Nd co-doped Zn1-xCaxGa2O4 solid solutions. Such solid-solution is employed as an optimized host to take advantage of its characteristic trap site level to establish an electron reservoir and network parameters for the precipitation of activators Nd3+ and Cr3+. The results reveal that the strategy employed here has the great potential, as well as opens new opportunities for future new-wavelength, NIR phosphorescent phosphors fabrication with many potential multifunctional bio-imaging applications.

  18. Hybrid coordination-network-engineering for bridging cascaded channels to activate long persistent phosphorescence in the second biological window

    PubMed Central

    Qin, Xixi; Li, Yang; Zhang, Ruili; Ren, Jinjun; Gecevicius, Mindaugas; Wu, Yiling; Sharafudeen, Kaniyarakkal; Dong, Guoping; Zhou, Shifeng; Ma, Zhijun; Qiu, Jianrong

    2016-01-01

    We present a novel “Top-down” strategy to design the long phosphorescent phosphors in the second biological transparency window via energy transfer. Inherence in this approach to material design involves an ingenious engineering for hybridizing the coordination networks of hosts, tailoring the topochemical configuration of dopants, and bridging a cascaded tunnel for transferring the persistent energy from traps, to sensitizers and then to acceptors. Another significance of this endeavour is to highlight a rational scheme for functionally important hosts and dopants, Cr/Nd co-doped Zn1−xCaxGa2O4 solid solutions. Such solid-solution is employed as an optimized host to take advantage of its characteristic trap site level to establish an electron reservoir and network parameters for the precipitation of activators Nd3+ and Cr3+. The results reveal that the strategy employed here has the great potential, as well as opens new opportunities for future new-wavelength, NIR phosphorescent phosphors fabrication with many potential multifunctional bio-imaging applications. PMID:26843129

  19. Coordinated Activation of Programmed Cell Death and Defense Mechanisms in Transgenic Tobacco Plants Expressing a Bacterial Proton Pump.

    PubMed Central

    Mittler, R.; Shulaev, V.; Lam, E.

    1995-01-01

    In plants, programmed cell death is thought to be activated during the hypersensitive response to certain avirulent pathogens and in the course of several differentiation processes. We describe a transgenic model system that mimics the activation of programmed cell death in higher plants. In this system, expression of a bacterial proton pump in transgenic tobacco plants activates a cell death pathway that may be similar to that triggered by recognition of an incompatible pathogen. Thus, spontaneous lesions that resemble hypersensitive response lesions are formed, multiple defense mechanisms are apparently activated, and systemic resistance is induced in the absence of a pathogen. Interestingly, mutation of a single amino acid in the putative channel of this proton pump renders it inactive with respect to lesion formation and induction of resistance to pathogen challenge. This transgenic model system may provide insights into the mechanisms involved in mediating cell death in higher plants. In addition, it may also be used as a general agronomic tool to enhance disease protection. PMID:12242350

  20. Insights into the emission reductions of multiple unintentional persistent organic pollutants from industrial activities.

    PubMed

    Liu, Guorui; Zheng, Minghui; Jiang, Xiaoxu; Jin, Rong; Zhao, Yuyang; Zhan, Jiayu

    2016-02-01

    Industrial activities result in unintentional production of multiple types of persistent organic pollutants (POPs) at various concentrations. Because of the potential adverse effect of these POPs on the environment, biota and human health, methods for controlling emission of POPs are required. Development and application of techniques for controlling emissions of POPs can be a technical and economic burden for the industry involved. Therefore, from the point of view of cost-benefit analysis, reducing emissions of multiple pollutants at the same time is optimal for sustainable industrial development. Although techniques have been developed for reducing the emissions of individual POPs, such as dioxins, further work is required on multi-POP control emissions from industrial activities. This paper discusses three important aspects that need to be taken to achieve multi-POP control. These aspects include the establishment of a comprehensive system for evaluating the risk from emissions of multiple POPs, determination of indicators for total emissions of multiple POPs, and the preparation and application of functional materials to inhibit formation of multiple POPs. These discussion might be helpful for the future research on the multi-POP control in industry.

  1. A Laboratory of Extremophiles: Iceland Coordination Action for Research Activities on Life in Extreme Environments (CAREX) Field Campaign

    PubMed Central

    Marteinsson, Viggó; Vaishampayan, Parag; Kviderova, Jana; Mapelli, Francesca; Medori, Mauro; Calfapietra, Carlo; Aguilera, Angeles; Hamisch, Domenica; Reynisson, Eyjólfur; Magnússon, Sveinn; Marasco, Ramona; Borin, Sara; Calzada, Abigail; Souza-Egipsy, Virginia; González-Toril, Elena; Amils, Ricardo; Elster, Josef; Hänsch, Robert

    2013-01-01

    Existence of life in extreme environments has been known for a long time, and their habitants have been investigated by different scientific disciplines for decades. However, reports of multidisciplinary research are uncommon. In this paper, we report an interdisciplinary three-day field campaign conducted in the framework of the Coordination Action for Research Activities on Life in Extreme Environments (CAREX) FP7EU program, with participation of experts in the fields of life and earth sciences. In situ experiments and sampling were performed in a 20 m long hot springs system of different temperature (57 °C to 100 °C) and pH (2 to 4). Abiotic factors were measured to study their influence on the diversity. The CO2 and H2S concentration varied at different sampling locations in the system, but the SO2 remained the same. Four biofilms, mainly composed by four different algae and phototrophic protists, showed differences in photosynthetic activity. Varying temperature of the sampling location affects chlorophyll fluorescence, not only in the microbial mats, but plants (Juncus), indicating selective adaptation to the environmental conditions. Quantitative polymerase chain reaction (PCR), DNA microarray and denaturing gradient gel electrophoresis (DGGE)-based analysis in laboratory showed the presence of a diverse microbial population. Even a short duration (30 h) deployment of a micro colonizer in this hot spring system led to colonization of microorganisms based on ribosomal intergenic spacer (RISA) analysis. Polyphasic analysis of this hot spring system was possible due to the involvement of multidisciplinary approaches. PMID:25371340

  2. A Two-Step Mechanism for Cell Fate Decision by Coordination of Nuclear and Mitochondrial p53 Activities

    PubMed Central

    Tian, Xiao-Jun; Liu, Feng; Zhang, Xiao-Peng; Li, Jun; Wang, Wei

    2012-01-01

    The tumor suppressor p53 has a crucial role in the DNA damage response. Here, we proposed an integrated model of the p53 network and explored how the nuclear and mitochondrial p53 pathways are coordinated to determine cell fates after -irradiation in radiosensitive tissues. Using numerical simulations, we found that depending on the extent of DNA damage, cells may survive, commit apoptosis after cell cycle arrest, or undergo apoptosis soon after irradiation. There exists a large cell-to-cell variability in outcome because of stochasticity in the generation and repair of DNA damage as well as cellular heterogeneity. At the cell population level, there occur two waves of apoptosis: a fast wave mediated by mitochondrial p53 within three hours postirradiation, and a slow wave mediated by nuclear p53 after eight hours postirradiation. Thus, we propose a two-step mechanism for cell fate decision. The first step is to decide whether DNA damage is severe enough to trigger apoptosis directly through the mitochondrial p53 pathway, while the second step is to determine whether the damage is fixed after cell cycle arrest. Such a mechanism may represent an efficient and reliable control mode, avoiding unnecessary death or greatly promoting the execution of apoptosis. It was also demonstrated that nuclear p53 can inhibit the pro-apoptotic activity of mitochondrial p53 by transactivating p21, and Mdm2 can facilitate apoptosis by promoting the mono-ubiquitination of p53. These results are either in good agreement with experimental observations or experimentally testable. Our work suggests that both the transcription-independent and -dependent p53 activities are indispensable for a reliable choice of cell fate and also provides clues to therapeutic manipulation of the p53 pathway in cancer treatment. PMID:22679490

  3. The Use of Multiple Slate Devices to Support Active Reading Activities

    ERIC Educational Resources Information Center

    Chen, Nicholas Yen-Cherng

    2012-01-01

    Reading activities in the classroom and workplace occur predominantly on paper. Since existing electronic devices do not support these reading activities as well as paper, users have difficulty taking full advantage of the affordances of electronic documents. This dissertation makes three main contributions toward supporting active reading…

  4. Patterns of cortico-limbic activations during visual processing of sad faces in depression patients: a coordinate-based meta-analysis.

    PubMed

    Lai, Chien-Han

    2014-01-01

    The author retrieved 10 functional magnetic resonance imaging studies about visual tasks for emotional faces in subjects with depression. The activation foci were then summarized and entered into a coordinate-based meta-analysis. The depression group showed significantly increased activations in the left striatum and left parahippocampal gyrus; the control group showed increased activations in the left medial frontal gyrus, left middle frontal gyrus, right thalamus, left anterior cingulate, and superior frontal gyrus. The study suggests that depression patients have limbic activations, and controls have fronto-thalamic activations with visual processing of emotional faces.

  5. Cellulase occurs in multiple active forms in ripe avocado fruit mesocarp.

    PubMed

    Kanellis, A K; Kalaitzis, P

    1992-02-01

    The existence of multiple forms of avocado (Persea americana Mill. cv Hass) cellulase in crude protein extracts of ripe avocado fruit is reported. Cellulase was separated into at least 11 multiple forms by native isoelectric focusing in the pH range between 4 and 7 and visualized by both activity staining using Congo red and immunostaining. The enzyme components were acidic proteins with isoelectric points in the range of pH 5.10 to 6.80, the predominant forms having isoelectric points of 5.60, 5.80, 5.95, and 6.20. All 11 forms were immunologically related with molecular masses of 54 kilodaltons.

  6. Semi-active control of a cable-stayed bridge under multiple-support excitations.

    PubMed

    Dai, Ze-Bing; Huang, Jin-Zhi; Wang, Hong-Xia

    2004-03-01

    This paper presents a semi-active strategy for seismic protection of a benchmark cable-stayed bridge with consideration of multiple-support excitations. In this control strategy, Magnetorheological (MR) dampers are proposed as control devices, a LQG-clipped-optimal control algorithm is employed. An active control strategy, shown in previous researches to perform well at controlling the benchmark bridge when uniform earthquake motion was assumed, is also used in this study to control this benchmark bridge with consideration of multiple-support excitations. The performance of active control system is compared to that of the presented semi-active control strategy. Because the MR fluid damper is a controllable energy- dissipation device that cannot add mechanical energy to the structural system, the proposed control strategy is fail-safe in that bounded-input, bounded-output stability of the controlled structure is guaranteed. The numerical results demonstrated that the performance of the presented control design is nearly the same as that of the active control system; and that the MR dampers can effectively be used to control seismically excited cable-stayed bridges with multiple-support excitations.

  7. Semi-active control of a cable-stayed bridge under multiple-support excitations.

    PubMed

    Dai, Ze-Bing; Huang, Jin-Zhi; Wang, Hong-Xia

    2004-03-01

    This paper presents a semi-active strategy for seismic protection of a benchmark cable-stayed bridge with consideration of multiple-support excitations. In this control strategy, Magnetorheological (MR) dampers are proposed as control devices, a LQG-clipped-optimal control algorithm is employed. An active control strategy, shown in previous researches to perform well at controlling the benchmark bridge when uniform earthquake motion was assumed, is also used in this study to control this benchmark bridge with consideration of multiple-support excitations. The performance of active control system is compared to that of the presented semi-active control strategy. Because the MR fluid damper is a controllable energy- dissipation device that cannot add mechanical energy to the structural system, the proposed control strategy is fail-safe in that bounded-input, bounded-output stability of the controlled structure is guaranteed. The numerical results demonstrated that the performance of the presented control design is nearly the same as that of the active control system; and that the MR dampers can effectively be used to control seismically excited cable-stayed bridges with multiple-support excitations. PMID:14727308

  8. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

    PubMed

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

    2016-01-28

    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. PMID:26655063

  9. Nordihydroguaiaretic Acid Inhibits an Activated FGFR3 Mutant, and Blocks Downstream Signaling in Multiple Myeloma Cells

    PubMed Central

    Meyer, April N.; McAndrew, Christopher W.; Donoghue, Daniel J.

    2008-01-01

    Activating mutations within Fibroblast Growth Factor Receptor 3 (FGFR3), a receptor tyrosine kinase, are responsible for human skeletal dysplasias including achondroplasia and the neonatal lethal syndromes, Thanatophoric Dysplasia (TD) type I and II. Several of these same FGFR3 mutations have also been identified somatically in human cancers, including multiple myeloma, bladder carcinoma and cervical cancer. Based on reports that strongly activated mutants of FGFR3 such as the TDII (K650E) mutant signal preferentially from within the secretory pathway, the inhibitory properties of nordihydroguaiaretic acid (NDGA), which blocks protein transport through the Golgi, were investigated. NDGA was able to inhibit FGFR3 autophosphorylation both in vitro and in vivo. In addition, signaling molecules downstream of FGFR3 activation such as STAT1, STAT3 and MAPK were inhibited by NDGA treatment. Using HEK293 cells expressing activated FGFR3-TDII, together with several multiple myeloma cell lines expressing activated forms of FGFR3, NDGA generally resulted in a decrease in MAPK activation by 1 hour, and resulted in increased apoptosis over 24 hours. The effects of NDGA on activated FGFR3 derivatives targeted either to the plasma membrane or the cytoplasm were also examined. These results suggest that inhibitory small molecules such as NDGA that target a specific subcellular compartment may be beneficial in the inhibition of activated receptors such as FGFR3 that signal from the same compartment. PMID:18794123

  10. L- and D-proline thiosemicarbazone conjugates: coordination behavior in solution and the effect of copper(II) coordination on their antiproliferative activity.

    PubMed

    Milunovic, Miljan N M; Enyedy, Éva A; Nagy, Nóra V; Kiss, Tamás; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K; Krachler, Regina; Novitchi, Ghenadie; Arion, Vladimir B

    2012-09-01

    Two enantiomerically pure thiosemicarbazone-proline conjugates with enhanced aqueous solubility, namely, 2-hydroxy-3-methyl-(S)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [L-Pro-STSC or (S)-H(2)L] and 2-hydroxy-3-methyl-(R)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [D-Pro-STSC or (R)-H(2)L] have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-vis and (1)H and (13)C NMR), and electrospray ionization mass spectrometry. The metal complexation behavior of L-Pro-STSC, stoichiometry, and thermodynamic stability of iron(II), iron(III), copper(II), and zinc(II) complexes in 30% (w/w) dimethyl sulfoxide/H(2)O solvent mixture have been studied by pH-potentiometric, UV-vis-spectrophotometric, circular dichroism, electron paramagnetic resonance, (1)H NMR spectroscopic, and spectrofluorimetric measurements. By the reaction of CuCl(2)·2H(2)O with (S)-H(2)L and (R)-H(2)L, respectively, the complexes [Cu[(S)-H(2)L]Cl]Cl and [Cu[(R)-H(2)L]Cl]Cl have been prepared and comprehensively characterized. An X-ray diffraction study of [Cu[(R)-H(2)L]Cl]Cl showed the formation of a square-planar copper(II) complex, which builds up stacks with interplanar separation of 3.3 Å. The antiproliferative activity of two chiral ligands and their corresponding copper(II) complexes has been tested in two human cancer cell lines, namely, SW480 (colon carcinoma) and CH1 (ovarian carcinoma). The thiosemicarbazone-proline conjugates L- and D-Pro-STSC show only moderate cytotoxic potency with IC(50) values of 62 and 75 μM, respectively, in CH1 cells and >100 μM in SW480 cells. However, the corresponding copper(II) complexes are 13 and 5 times more potent in CH1 cells, based on a comparison of IC(50) values, and in SW480 cells the increase in the antiproliferative activity is even higher. In both tested cell lines, L-Pro-STSC as well as its copper(II) complex show slightly stronger antiproliferative activity than the

  11. L- and D-proline thiosemicarbazone conjugates: coordination behavior in solution and the effect of copper(II) coordination on their antiproliferative activity.

    PubMed

    Milunovic, Miljan N M; Enyedy, Éva A; Nagy, Nóra V; Kiss, Tamás; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K; Krachler, Regina; Novitchi, Ghenadie; Arion, Vladimir B

    2012-09-01

    Two enantiomerically pure thiosemicarbazone-proline conjugates with enhanced aqueous solubility, namely, 2-hydroxy-3-methyl-(S)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [L-Pro-STSC or (S)-H(2)L] and 2-hydroxy-3-methyl-(R)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [D-Pro-STSC or (R)-H(2)L] have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-vis and (1)H and (13)C NMR), and electrospray ionization mass spectrometry. The metal complexation behavior of L-Pro-STSC, stoichiometry, and thermodynamic stability of iron(II), iron(III), copper(II), and zinc(II) complexes in 30% (w/w) dimethyl sulfoxide/H(2)O solvent mixture have been studied by pH-potentiometric, UV-vis-spectrophotometric, circular dichroism, electron paramagnetic resonance, (1)H NMR spectroscopic, and spectrofluorimetric measurements. By the reaction of CuCl(2)·2H(2)O with (S)-H(2)L and (R)-H(2)L, respectively, the complexes [Cu[(S)-H(2)L]Cl]Cl and [Cu[(R)-H(2)L]Cl]Cl have been prepared and comprehensively characterized. An X-ray diffraction study of [Cu[(R)-H(2)L]Cl]Cl showed the formation of a square-planar copper(II) complex, which builds up stacks with interplanar separation of 3.3 Å. The antiproliferative activity of two chiral ligands and their corresponding copper(II) complexes has been tested in two human cancer cell lines, namely, SW480 (colon carcinoma) and CH1 (ovarian carcinoma). The thiosemicarbazone-proline conjugates L- and D-Pro-STSC show only moderate cytotoxic potency with IC(50) values of 62 and 75 μM, respectively, in CH1 cells and >100 μM in SW480 cells. However, the corresponding copper(II) complexes are 13 and 5 times more potent in CH1 cells, based on a comparison of IC(50) values, and in SW480 cells the increase in the antiproliferative activity is even higher. In both tested cell lines, L-Pro-STSC as well as its copper(II) complex show slightly stronger antiproliferative activity than the

  12. Activity monitoring and motion classification of the lizard Chamaeleo jacksonii using multiple Doppler radars.

    PubMed

    Singh, Aditya; Lee, Scott S K; Butler, Marguerite; Lubecke, Victor

    2012-01-01

    We describe a simple, non-contact and efficient tool for monitoring the natural activity of a small lizard (Chamaeleo jacksonii) to yield valuable information about their metabolic activity and energy expenditure. It allows monitoring in a non-confined laboratory environment and uses multiple Doppler radars operating at 10.525 GHz. We developed a classification algorithm that can differentiate between fidgeting and locomotion by processing the quadrature baseband signals from the radars. The results have been verified by visual inspection and indicate that the tool could also be used for automated monitoring of the activities of reptiles and other small animals. PMID:23366934

  13. Activity monitoring and motion classification of the lizard Chamaeleo jacksonii using multiple Doppler radars.

    PubMed

    Singh, Aditya; Lee, Scott S K; Butler, Marguerite; Lubecke, Victor

    2012-01-01

    We describe a simple, non-contact and efficient tool for monitoring the natural activity of a small lizard (Chamaeleo jacksonii) to yield valuable information about their metabolic activity and energy expenditure. It allows monitoring in a non-confined laboratory environment and uses multiple Doppler radars operating at 10.525 GHz. We developed a classification algorithm that can differentiate between fidgeting and locomotion by processing the quadrature baseband signals from the radars. The results have been verified by visual inspection and indicate that the tool could also be used for automated monitoring of the activities of reptiles and other small animals.

  14. Modifications of laccase activities of copper efflux oxidase, CueO by synergistic mutations in the first and second coordination spheres of the type I copper center.

    PubMed

    Kataoka, Kunishige; Kogi, Hiroki; Tsujimura, Seiya; Sakurai, Takeshi

    2013-02-15

    The redox potential of type I copper in the Escherichia coli multicopper oxidase CueO was shifted in the positive or negative direction as a result of the single, double, and triple mutations in the first and second coordination spheres: the formation of the NH···S(-)(Cys500 ligand) hydrogen bond, the breakdown of the NH(His443 ligand)···O(-)(Asp439) hydrogen bond, and the substitution of the Met510 ligand for the non-coordinating Leu or coordinating Gln. Laccase activities of CueO were maximally enhanced 140-fold by virtue of the synergistic effect of mild mutations at and at around the ligand groups to type I copper.

  15. CALCULATING SEPARATE MAGNETIC FREE ENERGY ESTIMATES FOR ACTIVE REGIONS PRODUCING MULTIPLE FLARES: NOAA AR11158

    SciTech Connect

    Tarr, Lucas; Longcope, Dana; Millhouse, Margaret

    2013-06-10

    It is well known that photospheric flux emergence is an important process for stressing coronal fields and storing magnetic free energy, which may then be released during a flare. The Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) captured the entire emergence of NOAA AR 11158. This region emerged as two distinct bipoles, possibly connected underneath the photosphere, yet characterized by different photospheric field evolutions and fluxes. The combined active region complex produced 15 GOES C-class, two M-class, and the X2.2 Valentine's Day Flare during the four days after initial emergence on 2011 February 12. The M and X class flares are of particular interest because they are nonhomologous, involving different subregions of the active region. We use a Magnetic Charge Topology together with the Minimum Current Corona model of the coronal field to model field evolution of the complex. Combining this with observations of flare ribbons in the 1600 A channel of the Atmospheric Imaging Assembly on board SDO, we propose a minimization algorithm for estimating the amount of reconnected flux and resulting drop in magnetic free energy during a flare. For the M6.6, M2.2, and X2.2 flares, we find a flux exchange of 4.2 Multiplication-Sign 10{sup 20} Mx, 2.0 Multiplication-Sign 10{sup 20} Mx, and 21.0 Multiplication-Sign 10{sup 20} Mx, respectively, resulting in free energy drops of 3.89 Multiplication-Sign 10{sup 30} erg, 2.62 Multiplication-Sign 10{sup 30} erg, and 1.68 Multiplication-Sign 10{sup 32} erg.

  16. Pots and Pans Activities for Parent and Child: Activities for Preschool Multiple Handicapped Children.

    ERIC Educational Resources Information Center

    Van Tassel, Jean

    Intended for parents and teachers of multiply handicapped preschool children, the booklet provides lesson plans in three major areas--basic concepts, motor activities, and language activities. Each lesson plan is broken down into four parts: purpose (a descriptive statement of what the lesson hopes to accomplish), materials (list of materials…

  17. Multitype Activity Coexistence in an Inertial Two-Neuron System with Multiple Delays

    NASA Astrophysics Data System (ADS)

    Song, Zigen; Xu, Jian; Zhen, Bin

    2015-12-01

    In this paper, an inertial two-neuron system with multiple delays is analyzed to exhibit the effect of time delays on system dynamics. The parameter region with multiple equilibria is obtained employing the pitchfork bifurcation of trivial equilibrium. The stability analysis illustrates that two nontrivial equilibria are both stable for any delays. It implies that the neural system exhibits a stability coexistence of two resting states. Further, due to the existence of multiple delays, the neural system has a periodic activity around the trivial equilibrium via Hopf bifurcation. Finally, numerical simulations are employed to illustrate many richness coexistence for multitype activity patterns. Employing the period-adding route and fold bifurcation of periodic orbit, the neural system may have multistability coexistence of two resting states, two ASP-3s (anti-symmetric periodic activity with period three), one SSP-1 (self-symmetric periodic activity with period one), and one quasi-periodic spiking. Additionally, with increasing delay, quasi-periodic spiking evolves into chaos behavior.

  18. Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis.

    PubMed

    Peferoen, Laura A N; Vogel, Daphne Y S; Ummenthum, Kimberley; Breur, Marjolein; Heijnen, Priscilla D A M; Gerritsen, Wouter H; Peferoen-Baert, Regina M B; van der Valk, Paul; Dijkstra, Christine D; Amor, Sandra

    2015-01-01

    Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.

  19. Planning activities in space

    NASA Technical Reports Server (NTRS)

    Chang, Kai-Hsiung

    1987-01-01

    Three aspects of planning activities in space are presented. These include generating plans efficiently, coordinating actions among multiple agents, and recovering from plan execution errors. Each aspect is discussed separately.

  20. Reverse Monte Carlo Modeling of Pair Distribution Function Data as a Tool for Separating the Coordination Environments of Multiple Atoms Disordered Over a Single Site

    NASA Astrophysics Data System (ADS)

    King, Graham; Llobet, Anna; Ricciardo, Rebecca; Soliz, Jennifer; Woodward, Patrick; Ramezanipour, Farshid; Greedan, John

    2012-02-01

    The local structures of 8 perovskite compounds which contain equal concentrations of 2 transition metal cations disordered over the B-sites have been investigated using reverse Monte Carlo (RMC) modeling of neutron pair distribution function (PDF) data. Such compounds are known to display a number of interesting magnetic and electronic properties which, due to the cation disorder, cannot be correlated with the average long range structure and so remain poorly understood. In compounds with B=Mn/Ru there exists a valence degeneracy between Mn^3+/Ru^5+ and Mn^4+/Ru^4+. We demonstrate that the RMC method can be used as an effective tool to separate out the individual coordination environments of these cations and also to monitor the relative concentrations of the different oxidation states. We find that the valency ratio is governed by the size of the A-site cations. In a different series of Sr2FeMnO6-x perovskites we find that locally the structures are quite different from the average cubic structures, with the local coordination environments more closely resembling those of the brownmillerite structure. In all compounds the octahedra containing Mn^3+ are Jahn-Teller distorted, even if this distortion is not evident in the average structure.

  1. The Use of the Active Breathing Coordinator Throughout Radical Non-Small-Cell Lung Cancer (NSCLC) Radiotherapy

    SciTech Connect

    Brock, Juliet; McNair, Helen A.; Panakis, Niki; Symonds-Tayler, Richard; Evans, Phil M.; Brada, Michael

    2011-10-01

    Purpose: To assess feasibility and reproducibility of an Active Breathing Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung cancer, and compare lung dosimetric parameters between free-breathing and ABC plans. Methods and Materials: A total of 18 patients, recruited into an approved study, had free-breathing and ABC breath-hold treatment plans generated. Lung volume, the percentage volume of lung treated to a dose of {>=}20 Gy (V{sub 20}), and mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5 days/week) was delivered in breath-hold. Repeat breath-hold computed tomography scans were used to assess change in gross tumor volume (GTV) size and position. Setup error was also measured and potential GTV-planning target volume (PTV) margins calculated. Results: Seventeen of 18 patients completed radiotherapy using ABC daily. Intrafraction tumor position was consistent, but interfraction variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions, respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction in GTV from planning to end of treatment was 25% (p = 0.003). Potentially required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions. ABC reduced V{sub 20} by 13% (p = 0.0001), V{sub 13} by 12% (p = 0.001), and MLD by 13% (p < 0.001) compared with free-breathing; lung volume increased by 41% (p < 0.001). Conclusions: Clinically significant movements of GTV were seen during radiotherapy for non-small-cell lung cancer using ABC. Image guidance is recommended with ABC. The use of ABC can reduce dose volume parameters determining lung toxicity, and might allow for equitoxic radiotherapy dose escalation.

  2. ∆Np73 is capable of inducing apoptosis by co-ordinately activating several BH3-only proteins

    PubMed Central

    Sánchez-Carrera, Dámaso; García-Puga, Mikel; Yáñez, Lucrecia; Romón, Íñigo; Pipaón, Carlos

    2015-01-01

    Inactivation of p53 is one of the most relevant events in human cancer, since it allows transformed cells to escape their own proliferation control and leave them irresponsive to drugs that aim to damage their DNA. When p53 falls, other members of its family may become targets to attack tumoural cells. p73 has shown capacity to mediate these attacks. However, its N-terminal truncated isoforms have been associated with oncogenesis due to their capacity to act as dominant negatives of p53 and the transactivation (TA) isoforms of p73. We previously found a relationship between the overexpression of N-terminus-truncated p73 isoform (∆Np73) and that of the proapoptotic gene Bcl-2-interacting killer (BIK). In the present report we demonstrate that ∆Np73-α has the capacity to induce apoptosis through the co-ordinated activation of a group of genes harbouring GC-rich elements in their regulatory regions. ∆Np73-α synergizes with specificity protein (Sp1) on these elements but the overall response of these genes probably depends on the additional presence of consensus p53 elements. We explore the domains of ∆Np73-α involved in this transactivation capacity and found divergences with the previously described functions for them. Moreover, we found that the transforming mutation V12 of HRas impairs this transactivation capacity of ∆Np73-α, further supporting the anti-tumoural function of this later. Our data add complexity to the action of p73 on the induction of apoptosis and tumourogenesis, opening new interpretations to the expression profile of p73 isoforms in different human neoplasias. PMID:26182360

  3. Pleiotropic Activities of Vitamin D Receptors - Adequate Activation for Multiple Health Outcomes.

    PubMed

    Ryan, Jackson W; Anderson, Paul H; Morris, Howard A

    2015-05-01

    The vitamin D receptor (VDR), a nuclear transcription factor, elicits physiological regulation of gene transcription following binding of its ligand, 1,25-dihydroxyvitamin D. The major biological activities of vitamin D contribute to regulation of plasma calcium and phosphate homeostasis and bone remodeling, although recent evidence suggests that vitamin D, like other steroid hormone receptors, can regulate a diverse range of biological activities across many tissues. Such properties raise the notion that vitamin D deficiency may not only be detrimental to bone and muscular health, but also a risk factor for a number of adverse health outcomes including increased risk of cardiovascular disease, inflammation, immune system disorders and cancer. Advances in transcriptional research provide data not only on ligand-dependent activities of the VDR, but other activities of vitamin D extending to rapid modulation of intra-cellular signaling pathways as well as apparent ligand-independent interactions between the VDR and other transcriptionally active proteins. In this review, we detail the chief molecular activities of the VDR in regulating gene transcription, intracellular signaling and actions of VDR via binding to transcriptional regulating proteins. The breadth of biological activities attributed to vitamin D informs clinical biochemists and health care professionals on the implications of vitamin D deficiency for health. PMID:26224895

  4. Perspectives on Physical Activity Among People with Multiple Sclerosis Who Are Wheelchair Users

    PubMed Central

    Learmonth, Yvonne C.; Rice, Ian M.; Ostler, Teresa; Rice, Laura A.

    2015-01-01

    Background: People with advanced multiple sclerosis (MS) are less physically active than those with milder forms of the disease, and wheelchair use has a negative association with physical activity participation. Thus, wheelchair users with MS are doubly disadvantaged for accruing the benefits of physical activity and exercise. Appropriate physical activity and exercise interventions are needed for this population. Methods: We undertook a qualitative study to explore the meanings, motivations, and outcomes of physical activity in wheelchair users with MS. We sought to understand daily opportunities to accumulate physical activity and exercise, and to identify perceived barriers, facilitators, and benefits that might inform the design of future interventions. Results: We interviewed 15 wheelchair users (mean age, 52 ± 8.8 years; n = 12 women). Data were transcribed and analyzed to identify and explore common themes. Our first theme was the reduced opportunity to participate in physical activity due to participants' dependence on mobility devices, environmental adaptations, and tangible support. Our second theme was the importance of incorporating physical activity and exercise into the everyday environment, highlighting the need for adaptive exercise and accessible environments. This indicated the need to incorporate behavior change modulators into physical activity and exercise interventions for those with advanced MS. Health-care professionals played an important role in promoting increased physical activity and exercise participation in those with advanced MS. Conclusions: Our findings may inform future interventions to increase initiation and maintenance of physical activity and exercise among people with advanced MS. PMID:26052256

  5. A combined planning and self-efficacy intervention to promote physical activity: a multiple mediation analysis.

    PubMed

    Koring, Milena; Richert, Jana; Parschau, Linda; Ernsting, Anna; Lippke, Sonia; Schwarzer, Ralf

    2012-01-01

    Many individuals are motivated to improve their physical activity levels, but often fail to act upon their intention. Interventions fostering volitional strategies, such as action planning, coping planning, and self-efficacy beliefs, can help to translate intentions into behavior. This study examines the effectiveness and the mechanisms of a combined planning and self-efficacy intervention to promote physical activity among motivated individuals. Participants (N = 883) were randomly assigned to the intervention or to a waiting-list control condition. Multivariate analysis of variance revealed that the intervention resulted in significantly more physical activity, higher levels of action planning, coping planning, and volitional self-efficacy beliefs (p < 0.01). In addition, multiple mediation analysis showed that action planning, coping planning, and volitional self-efficacy mediate between the intervention and physical activity. The study shows that the intervention successfully fostered physical activity and unfolds the underlying self-regulatory mechanisms of the intervention's effectiveness.

  6. Factors That Moderate Activity Limitation and Participation Restriction in People With Multiple Sclerosis.

    PubMed

    Goverover, Yael; Strober, Lauren; Chiaravalloti, Nancy; DeLuca, John

    2015-01-01

    We examined the variables most associated with activity limitation (i.e., cooking) and participation restriction (i.e., employment) in 72 people with multiple sclerosis (MS). Participants underwent a comprehensive neuropsychological test battery assessing memory, executive functions, visual perception, and processing speed and completed questionnaires assessing activity, participation, fatigue, and affective symptoms. Results showed that processing speed was the only variable consistently significantly related to both activity and participation. When examining specific aspects of activity and participation in isolation, employment status was significantly associated with education level, visual memory, fatigue, and processing speed. Cooking ability was associated with performance on tasks of working memory, verbal memory, and processing speed. These findings suggest that processing speed is a primary cognitive factor in MS influencing quality of both activity and participation in everyday life. PMID:26122682

  7. Attributions and self-efficacy for physical activity in multiple sclerosis.

    PubMed

    Nickel, D; Spink, K; Andersen, M; Knox, K

    2014-01-01

    Self-efficacy is an important predictor of health-related physical activity in multiple sclerosis (MS). While past experiences are believed to influence efficacy beliefs, the explanations individuals provide for these experiences also may be critical. Our objective was to test the hypothesis that perceived success or failure to accumulate 150 min of physical activity in the previous week would moderate the relationship between the attributional dimension of stability and self-efficacy to exercise in the future. Forty-two adults with MS participated in this cross-sectional descriptive study. Participants completed questions assessing physical activity, perceived outcome for meeting the recommended level of endurance activity, attributions for the outcome, and exercise self-efficacy. Results from hierarchical multiple regression revealed a significant main effect for perceived outcome predicting self-efficacy that was qualified by a significant interaction. The final model, which included perceived outcome, stability, and the interaction term, predicted 37% of the variance in exercise self-efficacy, F (3, 38) = 7.27, p = .001. Our findings suggest that the best prediction of self-efficacy in the MS population may include the interaction of specific attributional dimensions with success/failure at meeting the recommended physical activity dose. Attributions may be another target for interventions aimed at increasing the physical activity in MS.

  8. Self-organising continuous attractor networks with multiple activity packets, and the representation of space.

    PubMed

    Stringer, S M; Rolls, E T; Trappenberg, T P

    2004-01-01

    'Continuous attractor' neural networks can maintain a localised packet of neuronal activity representing the current state of an agent in a continuous space without external sensory input. In applications such as the representation of head direction or location in the environment, only one packet of activity is needed. For some spatial computations a number of different locations, each with its own features, must be held in memory. We extend previous approaches to continuous attractor networks (in which one packet of activity is maintained active) by showing that a single continuous attractor network can maintain multiple packets of activity simultaneously, if each packet is in a different state space or map. We also show how such a network could by learning self-organise to enable the packets in each space to be moved continuously in that space by idiothetic (motion) inputs. We show how such multi-packet continuous attractor networks could be used to maintain different types of feature (such as form vs colour) simultaneously active in the correct location in a spatial representation. We also show how high-order synapses can improve the performance of these networks, and how the location of a packet could be read by motor networks. The multiple packet continuous attractor networks described here may be used for spatial representations in brain areas such as the parietal cortex and hippocampus.

  9. Dynamical Behaviors of Multiple Equilibria in Competitive Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing

    2016-03-01

    This paper addresses the problem of coexistence and dynamical behaviors of multiple equilibria for competitive neural networks. First, a general class of discontinuous nonmonotonic piecewise linear activation functions is introduced for competitive neural networks. Then based on the fixed point theorem and theory of strict diagonal dominance matrix, it is shown that under some conditions, such n -neuron competitive neural networks can have 5(n) equilibria, among which 3(n) equilibria are locally stable and the others are unstable. More importantly, it is revealed that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibria and locally stable equilibria than the ones with other activation functions, such as the continuous Mexican-hat-type activation function and discontinuous two-level activation function. Furthermore, the 3(n) locally stable equilibria given in this paper are located in not only saturated regions, but also unsaturated regions, which is different from the existing results on multistability of neural networks with multiple level activation functions. A simulation example is provided to illustrate and validate the theoretical findings.

  10. F+ tunable laser activity and interaction of atomic halogens (F, Cl and Br) at the low coordinated surface sites of SrOAb initio and DFT calculations.

    PubMed

    Shalabi, Ahmed S

    2002-10-01

    The twofold potential of F+ color centers at the low coordinated surfaces of SrO for providing tunable laser activity and adsorption properties for atomic halogens (F, Cl and Br) has been investigated using ab initio electronic structure calculations. SrO clusters of variable sizes were embedded in simulated Coulomb fields that closely approximate the Madelung fields of the host surfaces and the nearest neighbor ions to F+ were allowed to relax to equilibrium. Based on Stokes shifted optical transition bands and horizontal shifts along the configuration coordinate diagrams, the F+ laser activity was found to decrease as the coordination number of the surface ions decreases from 5 (flat) to 4 (edge) to 3 (corner). An attempt has been made to explain this result in terms of Madelung potentials and optical-optical conversion efficiencies. All relaxed excited states are deep below the conduction bands of the perfect ground states, implying that F+ is a laser-suitable defect. The most laser active flat surface is the least probable for relaxed excited state orientational destruction of F+. The excited state at the edge has the highest energy, implying exciton (energy) transfer to the flat and edge sites. F+ relaxation and defect-formation energies increase with increasing surface coordination number. The Glasner-Tompkins relation between the fundamental optical absorption of F+ in solids and the fundamental absorption of the host crystals can be generalized to include the low coordinated surfaces of SrO. The F+ color center changes the nature of halogen-surface interaction (adsorption energies) from physical adsorption to chemical adsorption. The halogen-surface interactions increase with increasing electronegativity of the halogen. The calculated adsorption energies can be explained in terms of surface electrostatic potentials, and the covalent spin pairing mechanism plays a dominant role in determining adsorbate-substrate interactions.

  11. Assisted ambulation and activities for persons with profound multiple disabilities: assessing different ambulation levels.

    PubMed

    Lancioni, G E; Mantini, M; Groeneweg, J

    2001-06-01

    Two participants with profound multiple disabilities were exposed to two occupational situations, which included 1-min. and 3-min. robot-assisted ambulation prior to each activity, respectively. Analysis showed participants' mean percentages of engagement time (session time they spent ambulating or manipulating objects) were well above 90 in both situations. The amount of deviant behavior was somewhat higher in the latter occupational situation for one participant. Implications of the findings were discussed.

  12. An Analysis Technique for Active Neutron Multiplicity Measurements Based on First Principles

    SciTech Connect

    Evans, Louise G; Goddard, Braden; Charlton, William S; Peerani, Paolo

    2012-08-13

    Passive neutron multiplicity counting is commonly used to quantify the total mass of plutonium in a sample, without prior knowledge of the sample geometry. However, passive neutron counting is less applicable to uranium measurements due to the low spontaneous fission rates of uranium. Active neutron multiplicity measurements are therefore used to determine the {sup 235}U mass in a sample. Unfortunately, there are still additional challenges to overcome for uranium measurements, such as the coupling of the active source and the uranium sample. Techniques, such as the coupling method, have been developed to help reduce the dependence of calibration curves for active measurements on uranium samples; although, they still require similar geometry known standards. An advanced active neutron multiplicity measurement method is being developed by Texas A&M University, in collaboration with Los Alamos National Laboratory (LANL) in an attempt to overcome the calibration curve requirements. This method can be used to quantify the {sup 235}U mass in a sample containing uranium without using calibration curves. Furthermore, this method is based on existing detectors and nondestructive assay (NDA) systems, such as the LANL Epithermal Neutron Multiplicity Counter (ENMC). This method uses an inexpensive boron carbide liner to shield the uranium sample from thermal and epithermal neutrons while allowing fast neutrons to reach the sample. Due to the relatively low and constant fission and absorption energy dependent cross-sections at high neutron energies for uranium isotopes, fast neutrons can penetrate the sample without significant attenuation. Fast neutron interrogation therefore creates a homogeneous fission rate in the sample, allowing for first principle methods to be used to determine the {sup 235}U mass in the sample. This paper discusses the measurement method concept and development, including measurements and simulations performed to date, as well as the potential

  13. Units Coordination and the Construction of Improper Fractions: A Revision of the Splitting Hypothesis

    ERIC Educational Resources Information Center

    Hackenberg, Amy J.

    2007-01-01

    This article communicates findings from a year-long constructivist teaching experiment about the relationship between four sixth-grade students' multiplicative structures and their construction of improper fractions. Students' multiplicative structures are the units coordinations that they can take as given prior to activity--i.e., the units…

  14. Multiple signaling pathways leading to the activation of interferon regulatory factor 3.

    PubMed

    Servant, Marc J; Grandvaux, Nathalie; Hiscott, John

    2002-09-01

    Virus infection of susceptible cells activates multiple signaling pathways that orchestrate the activation of genes, such as cytokines, involved in the antiviral and innate immune response. Among the kinases induced are the mitogen-activated protein (MAP) kinases, Jun-amino terminal kinases (JNK) and p38, the IkappaB kinase (IKK) and DNA-PK. In addition, virus infection also activates an uncharacterized VAK responsible for the C-terminal phosphorylation and subsequent activation of interferon regulatory factor 3 (IRF-3). Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity. The pathways leading to VAK activation are not well characterized, but IRF-3 appears to represent a novel cellular detection pathway that recognizes viral nucleocapsid (N) structure. Recently, the range of inducers responsible for IRF-3 activation has increased. In addition to virus infection, recognition of bacterial infection mediated through lipopolysaccharide by Toll-like receptor 4 has also been reported. Furthermore, MAP kinase kinase kinase (MAP KKK)-related pathways and DNA-PK induce N-terminal phosphorylation of IRF-3. This review summarizes recent observations in the identification of novel signaling pathways leading to IRF-3 activation.

  15. Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion.

    PubMed

    Raine, C S; Scheinberg, L; Waltz, J M

    1981-12-01

    Oligodendrocytes have been studied ultrastructurally in relationship to areas of active demyelination in multiple sclerosis. The tissue came from a central nervous system plaque sampled at biopsy during a neurosurgical procedure to correct severe intention tremor in a case of chronic progressive multiple sclerosis. Cells interpreted as oligodendrocytes were abundant within the demyelinated zone, were easily identifiable, and sometimes occurred as nests of cells suggestive of proliferation. Oligodendrocytes were also common within areas of active demyelination where numerous macrophages displayed active phagocytosis of myelin. These oligodendrocytes were paler and perhaps represented residual, surviving cells. In the relatively normal white matter adjacent to the plaque, increased numbers of oligodendrocytes occurred in association with remyelination. In the demyelinated zone, the astrocyte:macrophage:oligodendrocyte ratio was 1:2.25:4.5; within the region of ongoing demyelination, 1:4:4; and in the adjacent white matter, 1:0.1:2.1. On the basis of an apparent proliferation and survival of oligodendrocytes, the findings support the notions that there is no selective depletion of oligodendrocytes either during or shortly following central nervous system demyelination in multiple sclerosis, and that the myelin sheath is the primary target. PMID:7321526

  16. Activation of multiple mitogen-activated protein kinases by recombinant calcitonin gene-related peptide receptor.

    PubMed

    Parameswaran, N; Disa, J; Spielman, W S; Brooks, D P; Nambi, P; Aiyar, N

    2000-02-18

    Calcitonin gene-related peptide is a 37-amino-acid neuropeptide and a potent vasodilator. Although calcitonin gene-related peptide has been shown to have a number of effects in a variety of systems, the mechanisms of action and the intracellular signaling pathways, especially the regulation of mitogen-activated protien kinase (MAPK) pathway, is not known. In the present study we investigated the role of calcitonin gene-related peptide in the regulation of MAPKs in human embryonic kidney (HEK) 293 cells stably transfected with a recombinant porcine calcitonin gene-related peptide-1 receptor. Calcitonin gene-related peptide caused a significant dose-dependent increase in cAMP response and the effect was inhibited by calcitonin gene-related peptide(8-37), the calcitonin gene-related peptide-receptor antagonist. Calcitonin gene-related peptide also caused a time- and concentration-dependent increase in extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (P38 MAPK) activities, with apparently no significant change in cjun-N-terminal kinase (JNK) activity. Forskolin, a direct activator of adenylyl cyclase also stimulated ERK and P38 activities in these cells suggesting the invovement of cAMP in this process. Calcitonin gene-related peptide-stimulated ERK and P38 MAPK activities were inhibited significantly by calcitonin gene-related peptide receptor antagonist, calcitonin gene-related peptide-(8-37) suggesting the involvement of calcitonin gene-related peptide-1 receptor. Preincubation of the cells with the cAMP-dependent protein kinase inhibitor, H89 [¿N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride¿] inhibited calcitonin gene-related peptide-mediated activation of ERK and p38 kinases. On the other hand, preincubation of the cells with wortmannin ¿[1S-(1alpha,6balpha,9abeta,11alpha, 11bbeta)]-11-(acetyloxy)-1,6b,7,8,9a,10,11, 11b-octahydro-1-(methoxymethyl)-9a,11b-dimethyl-3H-furo[4,3, 2-de]indeno[4,5-h]-2

  17. Independent and Coordinate Effects of ADP-Ribosyltransferase and GTPase-Activating Activities of Exoenzyme S on HT-29 Epithelial Cell Function

    PubMed Central

    Fraylick, Jennifer E.; La Rocque, Jeannine R.; Vincent, Timothy S.; Olson, Joan C.

    2001-01-01

    Type III-mediated translocation of exoenzyme S (ExoS) into HT-29 epithelial cells by Pseudomonas aeruginosa causes complex alterations in cell function, including inhibition of DNA synthesis, altered cytoskeletal structure, loss of readherence, microvillus effacement, and interruption of signal transduction. ExoS is a bifunctional protein having both GTPase-activating (GAP) and ADP-ribosyltransferase (ADPRT) functional domains. Comparisons of alterations in HT-29 cell function caused by P. aeruginosa strains that translocate ExoS having GAP or ADPRT mutations allowed the independent and coordinate functions of the two activities to be assessed. An E381A ADPRT mutation revealed that ExoS ADPRT activity was required for effects of ExoS on DNA synthesis and long-term cell rounding. Conversely, the R146A GAP mutation appeared to have little impact on the cellular effects of ExoS. While transient cell rounding was detected following exposure to the E381A mutant, this rounding was eliminated by an E379A-E381A ADPRT double mutation, implying that residual ADPRT activity, rather than GAP activity, was effecting transient cell rounding by the E381A mutant. To explore this possibility, E381A and R146A-E381A mutants were examined for their ability to ADP-ribosylate Ras in vitro or in vivo. While no ADP-ribosylation of Ras was detected by either mutant in vitro, both mutants were able to modify Ras when translocated by the bacteria, with the R146A-E381A mutant causing more efficient modification than the E381A mutant, in association with increased inhibition of DNA synthesis. Comparisons of Ras ADP-ribosylation by wild-type and E381A mutant ExoS by two-dimensional electrophoresis found the former to ADP-ribosylate Ras at two sites, while the latter modified Ras only once. These studies draw attention to the key role of ExoS ADPRT activity in causing the effects of bacterially translocated ExoS on DNA synthesis and cell rounding. In addition, the studies provide insight into

  18. COORDINATED AV.

    ERIC Educational Resources Information Center

    CLEAVES, PAUL C.; AND OTHERS

    THE INSTRUCTIONAL MATERIALS CENTER IS LOCATED IN THE LOCAL HIGH SCHOOL AND SUPPLIES ALL SCHOOLS IN THE AREA. AUDIOVISUAL EQUIPMENT ORDERS, AFTER SELECTIONS ARE MADE BY THE CLASSROOM TEACHER, ARE PROCESSED BY THE CENTER, CONFIRMED AND DELIVERED BY TRUCK THREE TIMES EACH WEEK. EACH SCHOOL HAS A BUILDING COORDINATOR WHO CHECKS THE ORDERS INTO THE…

  19. Centrally patterned rhythmic activity integrated by a peripheral circuit linking multiple oscillators.

    PubMed

    Jellies, John; Kueh, Daniel

    2012-08-01

    The central pattern generator for heartbeat in the medicinal leech, Hirudo generates rhythmic activity conveyed by heart excitor motor neurons in segments 3-18 to coordinate the bilateral tubular hearts and side vessels. We focus on behavior and the influence of previously un-described peripheral nerve circuitry. Extracellular recordings from the valve junction (VJ) where afferent vessels join the heart tube were combined with optical recording of contractions. Action potential bursts at VJs occurred in advance of heart tube and afferent vessel contractions. Transections of nerves were performed to reduce the output of the central pattern generator reaching the heart tube. Muscle contractions persisted but with a less regular rhythm despite normal central pattern generator rhythmicity. With no connections between the central pattern generator and heart tube, a much slower rhythm became manifest. Heart excitor neuron recordings showed that peripheral activity might contribute to the disruption of centrally entrained contractions. In the model presented, peripheral activity would normally modify the activity actually reaching the muscle. We also propose that the fundamental efferent unit is not a single heart excitor neuron, but rather is a functionally defined unit of about three adjacent motor neurons and the peripheral assembly of coupled peripheral oscillators.

  20. Changes in cerebrospinal fluid levels of malondialdehyde and glutathione reductase activity in multiple sclerosis.

    PubMed

    Calabrese, V; Raffaele, R; Cosentino, E; Rizza, V

    1994-01-01

    The chemical composition of human cerebrospinal fluid (CSF) is considered to reflect brain metabolism. In this study we measured malondialdehyde (MDA) levels and the activity of enzymes involved in antioxidative processes, glutathione reductase and glutathione peroxidase, in human cerebrospinal fluid of multiple-sclerosis (MS) patients and normal healthy volunteers. Our results indicated that the cerebrospinal fluid in MS showed significantly higher endogenous levels of MDA than the control, as well as a much greater resistance to in-vitro stimulation test. In addition, we found the activity of GSH reductase significantly increased, about twice the control values, whereas the activity of glutathione peroxidase was markedly decreased as compared to control values. Our findings suggest that in MS the activity of antioxidant enzymes is modified, and indicates the conceivable possibility of a pathogenic role of oxidative stress in the determinism of the disease. PMID:7607784

  1. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    PubMed

    Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

    2015-01-01

    Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  2. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

    PubMed

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-07-02

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  3. Active Control of Turbulent Boundary Layer Induced Sound Radiation from Multiple Aircraft Panels

    NASA Technical Reports Server (NTRS)

    Gibbs, Gary P.; Cabell, Randolph H.

    2002-01-01

    The objective of this work is to experimentally investigate active structural acoustic control of turbulent boundary layer (TBL) induced sound radiation from multiple panels on an aircraft sidewall. One possible approach for controlling sound radiation from multiple panels is a multi-input/multi-output scheme which considers dynamic coupling between the panels. Unfortunately, this is difficult for more than a few panels, and is impractical for a typical aircraft which contains several hundred such panels. An alternative is to implement a large number of independent control systems. Results from the current work demonstrate the feasibility of reducing broadband radiation from multiple panels utilizing a single-input/single-output (SISO) controller per bay, and is the first known demonstration of active control of TBL induced sound radiation on more than two bays simultaneously. The paper compares sound reduction for fully coupled control of six panels versus independent control on each panel. An online adaptive control scheme for independent control is also demonstrated. This scheme will adjust for slow time varying dynamic systems such as fuselage response changes due to aircraft pressurization, etc.

  4. Active roll control for rollover prevention of heavy articulated vehicles with multiple-rollover-index minimisation

    NASA Astrophysics Data System (ADS)

    Huang, Hsun-Hsuan; Yedavalli, Rama K.; Guenther, Dennis A.

    2012-03-01

    This paper presents the application of a nominal control design algorithm for rollover prevention of heavy articulated vehicles with active anti-roll-bar control. This proposed methodology is based on an extension of linear quadratic regulator control for 'state derivative-induced (control coupled) output regulation' problems. For heavy articulated vehicles with multiple axles, a performance index with multiple rollover indices is proposed. The proposed methodology allows us to compare the usefulness of various control configurations (i.e. actuators at different axles of the vehicle) based on the interaction of this control configuration with vehicle dynamics. Application of this methodology to a specific heavy articulated vehicle with a tractor semi-trailer shows that a single active anti-roll-bar system at the trailer unit gives better performance than multiple-axle actuators at tractor and trailer together with the single lane change manoeuvre as the external disturbance. Thus, the proposed methodology of this paper not only highlights the importance of the interactions between control and vehicle dynamics in rollover prevention problems but, in fact, proposes a novel technique to exploit the benefits of these interactions judiciously.

  5. Multiple, Ligand-Dependent Routes from the Active Site of Cytochrome P450 2C9

    SciTech Connect

    Cojocaru, Vlad; Winn, Peter J.; Wade, Rebecca C.

    2012-02-13

    The active site of liver-specific, drug-metabolizing cytochrome P450 (CYP) monooxygenases is deeply buried in the protein and is connected to the protein surface through multiple tunnels, many of which were found open in different CYP crystal structures. It has been shown that different tunnels could serve as ligand passage routes in different CYPs. However, it is not understood whether one CYP uses multiple routes for substrate access and product release and whether these routes depend on ligand properties. From 300 ns of molecular dynamics simulations of CYP2C9, the second most abundant CYP in the human liver we found four main ligand exit routes, the occurrence of each depending on the ligand type and the conformation of the F-G loop, which is likely to be affected by the CYP-membrane interaction. A non-helical F-G loop favored exit towards the putative membrane-embedded region. Important protein features that direct ligand exit include aromatic residues that divide the active site and whose motions control access to two pathways. The ligands interacted with positively charged residues on the protein surface through hydrogen bonds that appear to select for acidic substrates. The observation of multiple, ligand-dependent routes in a CYP aids understanding of how CYP mutations affect drug metabolism and provides new possibilities for CYP inhibition.

  6. The coating of conducting copolymer on coordination polymer nanorod: A visible light active p-n heterojunction photocatalyst for H2 production

    NASA Astrophysics Data System (ADS)

    Jia, Yuan; Mei, Ming-liang; Xu, Xin-xin; Wang, Lin-shan

    2016-06-01

    A visible light active p-n heterojunction photocatalyst was synthesized successfully through in-situ chemical oxidation copolymerization of aniline (ANI) and diphenylamine-4-sulfonate (DPAS) with the existence of coordination polymer nanorod (CPNR) under initiation of ammonium persulfate (APS). Compared with neat coordination polymer nanorod, the resulted p-n heterojunction photocatalyst exhibits higher H2 generationrate under visible light irradiation. In this heterojunction photocatalyst, as a p-type semiconductor possessing suitable energy levels with coordination polymer nanorod, poly-(aniline-co-N-(4-sulfophenyl)-aniline) (PAPSA) forms p-n heterojunction with n-type coordination polymer nanorod, the inner electric field of p-n heterojunction accelerates the separation of electrons and holes, which enhances H2 production performance. Furthermore, the influence of concentration ratio between DPAS and ANI on photocatalytic property of the p-n heterojunction photocatalyst was discussed and a reasonable condition to fabricate photocatalyst with high H2 generationrate had been obtained. During photocatalytic water splitting H2 generation, the p-n heterojunction photocatalyst exhibited outstanding stability.

  7. The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma

    PubMed Central

    Spencer, Andrew; Yoon, Sung-Soo; Harrison, Simon J.; Morris, Shannon R.; Smith, Deborah A.; Brigandi, Richard A.; Gauvin, Jennifer; Kumar, Rakesh; Opalinska, Joanna B.

    2014-01-01

    The PI3K/AKT pathway is constitutively active in hematologic malignancies, providing proliferative and antiapoptotic signals and possibly contributing to drug resistance. We conducted an open-label phase 1 study to evaluate the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of afuresertib—an oral AKT inhibitor—in patients with advanced hematologic malignancies. Seventy-three patients were treated at doses ranging from 25 to 150 mg per day. The MTD was established at 125 mg per day because of 2 dose-limiting toxicities in the 150-mg cohort (liver function test abnormalities). The most frequent adverse events were nausea (35.6%), diarrhea (32.9%), and dyspepsia (24.7%). Maximum plasma concentrations and area under the plasma concentration-time curves from time 0 to 24 hours were generally dose proportional at >75-mg doses; the median time to peak plasma concentrations was 1.5 to 2.5 hours post dose, with a half-life of approximately 1.7 days. Three multiple myeloma patients attained partial responses; an additional 3 attained minimal responses. Clinical activity was also observed in non-Hodgkin lymphoma, Langerhan's cell histiocytosis, and Hodgkin disease. Single-agent afuresertib showed a favorable safety profile and demonstrated clinical activity against hematologic malignancies, including multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00881946. PMID:25075128

  8. Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

    PubMed

    Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

    2016-09-01

    The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

  9. Extraction of Neural Activity from In Vivo Optical Recordings Using Multiple Independent Component Analysis

    NASA Astrophysics Data System (ADS)

    Yoshida, Takamasa; Sakagami, Masanori; Yamazaki, Kyoko; Katura, Takusige; Iwamoto, Mitsumasa; Tanaka, Naoki

    A multiple independent component analysis (ICA) method based on the noisy time-delayed decorrelation algorithm is described that overcomes the problems and improves the usefulness of conventional ICA, which is commonly used for extracting the actual neural activity from data measured using optical recording with a voltage-sensitive dye to visualize neural activities in cortical areas as two-dimensional images. The problems with conventional ICA extraction include the lack of an a priori guarantee that the solution will be appropriate, the linear mixing of mutually independent random variables although the mixtures are not random variables but time signals in many applications, and the general requirement for repetitive calculation of large matrices. Application of multiple ICA to the extraction of neural activities in the guinea pig auditory cortex evoked by both click sounds and pure tones from optical recordings made using a voltage sensitive dye demonstrated that it effectively removes pulsatile and respiratory components from the measurement data and extracts neural activities from the optical recordings.

  10. Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

    PubMed Central

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe; Hesse, Dan; Lund, Henrik; Langkilde, Annika; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2012-01-01

    Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26high T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26high T cells, and the percentage of CD4+CD26high T cells that were CD49dhigh correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy. PMID:22701554

  11. Multiple Behavior Change in Diet and Activity: A Randomized Controlled Trial Using Mobile Technology

    PubMed Central

    Spring, Bonnie; Schneider, Kristin; McFadden, H.G.; Vaughn, Jocelyn; Kozak, Andrea T.; Smith, Malaina; Moller, Arlen C.; Epstein, Leonard H.; DeMott, Andrew; Hedeker, Donald; Siddique, Juned; Lloyd-Jones, Donald M.

    2012-01-01

    Background Many patients exhibit multiple chronic disease risk behaviors. Research provides little information about advice that can maximize simultaneous health behavior changes. Methods To test which combination of diet and activity advice maximizes healthy change, we randomized 204 adults with elevated saturated fat and low fruit/vegetable intakes, high sedentary leisure time and low physical activity to one of four treatments: increase fruit/vegetable and physical activity; decrease fat and sedentary leisure; decrease fat and increase physical activity; increase fruit/vegetable and decrease sedentary leisure. Treatments provided three weeks of remote coaching supported by mobile decision support technology and financial incentives. During treatment, incentives were contingent on using the mobile device to self-monitor and attain behavioral targets; during follow-up they were contingent only on recording. The outcome was standardized, composite improvement on the four diet and activity behaviors at end of treatment and five month follow-up. Results Of those randomized, 200 (98%) completed follow-up. The increase fruit/vegetable and decrease sedentary leisure treatment improved more than the other 3 treatments (p<.001). Specifically, fruit/vegetables increased from 1.2 servings/day to 5.5; sedentary leisure decreased from 219.2 minutes/day to 89.3; saturated fat decreased from 12.0% of calories consumed to 9.5%. Differences between treatment groups were maintained through follow-up. Traditional dieting (decrease fat and increase physical activity) improved less than the other 3 treatments (p<.001). Conclusions Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity. Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes. PMID:22636824

  12. Vegetation burned areas derived from multiple satellite-based active fires

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoyang; Kondragunta, Shobha

    2008-08-01

    Biomass burning releases a significant amount of trace gases and aerosol emissions into the atmosphere. If unaccounted for in the modeling of climate, carbon cycle, and air quality, it leads to large uncertainties. The amount of biomass burning emissions depends significantly on burned areas. This study estimates near-real time burned areas from multiple satellite-based active fires in Hazard Mapping System (HMS) developed in NOAA, which capitalizes automated fire detections from Geostationary Operational Environmental Satellite (GOES) Imager, Advanced Very High Resolution Radiometer (AVHRR), Moderate Resolution Imaging Spectroradiometer (MODIS). The HMS fire counts are compared with a set of Landsat ETM+ burn scars for various ecosystems to investigate the rate of burned area in a fire count. The fire size and fire duration derived from multiple satellites are then used to calculate burned area every half hour. The estimated burned areas are evaluated using national inventory of burned area across the United States for 2005.

  13. Estimation of the Performance of Multiple Active Neutron Interrogation Signatures for Detecting Shielded HEU

    SciTech Connect

    David L. Chichester; Scott J. Thompson; Scott M. Watson; James T. Johnson; Edward H. Seabury

    2012-10-01

    A comprehensive modeling study has been carried out to evaluate the utility of multiple active neutron interrogation signatures for detecting shielded highly enriched uranium (HEU). The modeling effort focused on varying HEU masses from 1 kg to 20 kg; varying types of shields including wood, steel, cement, polyethylene, and borated polyethylene; varying depths of the HEU in the shields, and varying engineered shields immediately surrounding the HEU including steel, tungsten, and cadmium. Neutron and gamma-ray signatures were the focus of the study and false negative detection probabilities versus measurement time were used as a performance metric. To facilitate comparisons among different approaches an automated method was developed to generate receiver operating characteristic (ROC) curves for different sets of model variables for multiple background count rate conditions. This paper summarizes results or the analysis, including laboratory benchmark comparisons between simulations and experiments. The important impact engineered shields can play towards degrading detectability and methods for mitigating this will be discussed.

  14. [Influence of coordination compounds of germanium (IV) and stannum (IV) on activity of some microbial enzymes with glycolytic and proteolytic action].

    PubMed

    Varbanets', L D; Matseliukh, O V; Nidialkova, N A; Hudzenko, O V; Avdiiuk, K V; Shmatkova, N V; Seĭfullina, I Ĭ

    2014-01-01

    Influence of coordinative compounds of germanium (IV) and stanum (IV) (complexes of germanium (IV) with nicotinamide (Nad) [GeCl2(Nad)4]Cl2 (1) and complexes of stanum (IV) with 2-hydroxybenzoilhydrazone 4-dimetylaminobenzaldehide (2-OH-HBdb) [SnCl4(2-OH-Bdb-H)] (2), 3-hydroxy-2-naphtoilhydrazone 2-hydroxynaphtaldehide (3-OH-H2Lnf) [SnCl3(3-OH-HLnf)] (3) and izonicotinoilhydrazone 2-hydroxyibenzaldehide [SnCl3 (Is·H)] (4) on activity of peptidases 1 and 2 Bacillus thuringiensis, α-L-rhamnosidase Cryptococcus albidus, Eupenicillium erubescens and α-amylase Aspergillus flavus var. oryzae. Results testify that all studied compounds differ on their influence on activity of the enzymes tested: significantly don't change elastolytic activity of peptidases 1 and 2 B. thuringiensis, completely inhibit A. flavus var. oryzae amylase, activate or oppress of α-L-rhamnosidase C. albidus and E. erubescens. Considerable differences in compounds (3, 4) on activity observed in case of the last. It's possible that peculiarity of influence (1) in compare with (2-4) is connected with existence of different central atoms of complexants: germanium (IV) (1) and stanum (IV) (2-4). A certain analogy in oppression of C. albidus α-L-rhamnosidase by compounds (1) and (4) can explain with presence of a pyridinic ring at molecules of their ligands. The less activsty displayed compound (2) with coordinative knot {SnCl4ON}. Nature of compounds (3, 4) activity was absolutely different: essential increase of activity of C. albidus α-L-rhamnosidase and full oppression of E. erubescens α-L-rhamnosidase by compound (3), while the action of compound (4) was feed back. Taking into account identical coordination knot {SnCl3O2N} the major role in this case play change of a hydrazide fragment in molecules of their ligands.

  15. Heparin derivatives for the targeting of multiple activities in the inflammatory response.

    PubMed

    Veraldi, Noemi; Hughes, Ashley J; Rudd, Timothy R; Thomas, Huw B; Edwards, Steven W; Hadfield, Lynsay; Skidmore, Mark A; Siligardi, Giuliano; Cosentino, Cesare; Shute, Janis K; Naggi, Annamaria; Yates, Edwin A

    2015-03-01

    An attractive strategy for ameliorating symptoms arising from the multi-faceted processes of excessive and/or continual inflammation would be to identify compounds able to interfere with multiple effectors of inflammation. The well-tolerated pharmaceutical, heparin, is capable of acting through several proteins in the inflammatory cascade, but its use is prevented by strong anticoagulant activity. Derivatives of heparin involving the periodate cleavage of 2,3 vicinal diols in non-sulfated uronate residues (glycol-split) and replacement of N-sulphamido- with N-acetamido- groups in glucosamine residues, capable of inhibiting neutrophil elastase activity in vitro, while exhibiting attenuated anticoagulant properties, have been identified and characterised. These also interact with two other important modulators of the inflammatory response, IL-8 and TNF-alpha. It is therefore feasible in principle to modulate several activities, while minimising anticoagulant side effects, providing a platform from which improved anti-inflammatory agents might be developed.

  16. Increasing Physical Activity and Participation in People With Multiple Sclerosis: A Review.

    PubMed

    Backus, Deborah

    2016-09-01

    Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system (CNS) affecting >2.5 million people worldwide. Damage to neurons in the CNS causes various sensorimotor and cognitive symptoms, such as fatigue, pain, spasticity, memory deficits, and impairment of mobility. Until the late 1990s, it was believed that symptoms of MS would be worsened with physical exertion and people with MS were encouraged to limit physical activity and exertion. Not only has emerging evidence suggested that physical activity, including exercise, is safe for people with MS, there is also evidence that at least some of the disability that occurs after MS is due to secondary deconditioning from the sedentary lifestyle adopted because of the symptoms of MS, not just CNS damage alone. Therefore, not only is physical activity safe, it is also required for maintaining function and health in people with MS. The purpose of this article is to review the unique physical and social barriers to physical activity in people with MS, including those with moderate to severe disability who use a wheelchair or scooter for mobility. We will discuss how existing guidelines for physical activity may not meet the needs of people with MS and present evidence-based considerations for promoting physical activity in people with MS. Ultimately, the goal is to overcome the barriers to physical activity and improve health, participation, and quality of life in people with MS. PMID:27211007

  17. Leisure time activities of Iranian patients with multiple sclerosis: a qualitative study

    PubMed Central

    Hosseini, Seyed Mohammad Sadegh; Asgari, Ali; Rassafiani, Mehdi; Yazdani, Farzaneh; Mazdeh, Mehrdokht

    2016-01-01

    Background: Leisure time is one of the most important aspects of life, especially for people with chronic diseases. The concept and types of leisure have frequently been evaluated in different socio-cultural populations. The aim of this study was to identify the nature of leisure activities among a sample of Iranian patients with multiple sclerosis (MS) and classify the identified types of activities in the context of Iranian culture. Methods: In this qualitative study, semi-structured interview was applied to gather data from 34 MS patients that were selected through purposive sampling. The interviews were continued up to the point of saturation. Content analysis was used to explore experiences of the interviewees regarding their leisure activities. Results: Six categories of leisure activities were extracted for the studied patients with MS i.e.physical, social, individual, art/cultural, educational and spiritual/religious. Conclusion: The results represented the range and heterogeneity of leisure activities amongst the MS patients. Considering participation in spiritual/religious and social activities as leisure time undertaking might reflect cultural diversity in the perception and use of time for recreation. For mental health promotion purposes, paying special attention to the types of activities that people of different socio-cultural background choose for their refreshment could help health care providers in giving tailored advice for patients with MS and other chronic debilitating disease. PMID:27123437

  18. A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects

    PubMed Central

    2014-01-01

    Background The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers. Results For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks. Conclusions Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing. PMID:24456150

  19. Evaluation of multiple-frequency, active and passive acoustics as surrogates for bedload transport

    USGS Publications Warehouse

    Wood, Molly S.; Fosness, Ryan L.; Pachman, Gregory; Lorang, Mark; Tonolla, Diego

    2015-01-01

    The use of multiple-frequency, active acoustics through deployment of acoustic Doppler current profilers (ADCPs) shows potential for estimating bedload in selected grain size categories. The U.S. Geological Survey (USGS), in cooperation with the University of Montana (UM), evaluated the use of multiple-frequency, active and passive acoustics as surrogates for bedload transport during a pilot study on the Kootenai River, Idaho, May 17-18, 2012. Four ADCPs with frequencies ranging from 600 to 2000 kHz were used to measure apparent moving bed velocities at 20 stations across the river in conjunction with physical bedload samples. Additionally, UM scientists measured the sound frequencies of moving particles with two hydrophones, considered passive acoustics, along longitudinal transects in the study reach. Some patterns emerged in the preliminary analysis which show promise for future studies. Statistically significant relations were successfully developed between apparent moving bed velocities measured by ADCPs with frequencies 1000 and 1200 kHz and bedload in 0.5 to 2.0 mm grain size categories. The 600 kHz ADCP seemed somewhat sensitive to the movement of gravel bedload in the size range 8.0 to 31.5 mm, but the relation was not statistically significant. The passive hydrophone surveys corroborated the sample results and could be used to map spatial variability in bedload transport and to select a measurement cross-section with moving bedload for active acoustic surveys and physical samples.

  20. Inhibition of intracellular proteolysis in muscle cultures by multiplication-stimulating activity

    NASA Technical Reports Server (NTRS)

    Janeczko, Richard A.; Etlinger, Joseph D.

    1984-01-01

    The effects of the insulin-like growth factor, multiplication-stimulating activity (MSA), on chick myotube cultures are studied. The results indicate that MSA is an effective anabolic agent regulating protein metabolism and amino acid uptake, but not sugar transport. Similar size effects on protein metabolism and amino acid uptake in serum-free media were observed in parallel studies with insulin, although insulin levels well in excess of the normal physiological range are required to produce significant effects. It is suggested that there is a generally low insulin sensitivity in cultured chick myotubes relative to adult tissues.

  1. Community Health Workers promoting physical activity: Targeting multiple levels of the Social Ecological Model

    PubMed Central

    Haughton, Jessica; Ayala, Guadalupe X.; Burke, Kari Herzog; Elder, John P.; Montañez, Jacqueline; Arredondo, Elva M.

    2015-01-01

    The effectiveness of Community Health Workers (CHWs) as health educators and health promoters among Latino populations is widely recognized. The Affordable Care Act created important opportunities to increase the role of CHWs in preventive health. This article describes the implementation of CHW-led, culturally specific, faith-based program to increase physical activity (PA) among churchgoing Latinas. The current study augments previous research by describing the recruitment, selection, training, and evaluation of CHWs for a PA intervention targeting multiple levels of the Social Ecological Model. PMID:26280587

  2. Silver-free activation of ligated gold(I) chlorides: the use of [Me3NB12Cl11]- as a weakly coordinating anion in homogeneous gold catalysis.

    PubMed

    Wegener, Michael; Huber, Florian; Bolli, Christoph; Jenne, Carsten; Kirsch, Stefan F

    2015-01-12

    Phosphane and N-heterocyclic carbene ligated gold(I) chlorides can be effectively activated by Na[Me3NB12Cl11] (1) under silver-free conditions. This activation method with a weakly coordinating closo-dodecaborate anion was shown to be suitable for a large variety of reactions known to be catalyzed by homogeneous gold species, ranging from carbocyclizations to heterocyclizations. Additionally, the capability of 1 in a previously unknown conversion of 5-silyloxy-1,6-allenynes was demonstrated.

  3. International Assistance for Low-Emission Development Planning: Coordinated Low Emissions Assistance Network (CLEAN) Inventory of Activities and Tools--Preliminary Trends

    SciTech Connect

    Cox, S.; Benioff, R.

    2011-05-01

    The Coordinated Low Emissions Assistance Network (CLEAN) is a voluntary network of international practitioners supporting low-emission planning in developing countries. The network seeks to improve quality of support through sharing project information, tools, best practices and lessons, and by fostering harmonized assistance. CLEAN has developed an inventory to track and analyze international technical support and tools for low-carbon planning activities in developing countries. This paper presents a preliminary analysis of the inventory to help identify trends in assistance activities and tools available to support developing countries with low-emission planning.

  4. Levels and Rates of Physical Activity in Older Adults with Multiple Sclerosis.

    PubMed

    Klaren, Rachel E; Sebastiao, Emerson; Chiu, Chung-Yi; Kinnett-Hopkins, Dominique; McAuley, Edward; Motl, Robert W

    2016-05-01

    There is much evidence supporting the safety and benefits of physical activity in adults with multiple sclerosis (MS) and recent evidence of beneficial effects on physical function in older adults with MS. However, there is very little known about physical activity participation in older adults with conditions such as MS. This study compared levels of physical activity (i.e., sedentary behavior, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA)) and rates of meeting public health guidelines for MVPA (i.e., ≥30 min/day) among young (i.e., ages 20-39 years), middle-aged (i.e., ages 40-59 years) and older adults (i.e., ages ≥60 years) with MS. The sample included 963 persons with MS who provided demographic and clinical information and wore an accelerometer for a 7-day period. The primary analysis involved a between-subjects ANOVA on accelerometer variables (i.e., accelerometer wear time; number of valid days; sedentary behavior in min/day; LPA in min/day; and MVPA in min/day). Collectively, our data indicated that older adults with MS engaged in less MVPA and more sedentary behavior than middle-aged and young adults with MS. Such results highlight the importance of developing physical activity interventions as an effective means for managing the progression and consequences of MS in older adults. PMID:27330842

  5. Physical Activity and Fatigue in Breast Cancer and Multiple Sclerosis: Psychosocial Mechanisms

    PubMed Central

    McAuley, Edward; White, Siobhan M.; Rogers, Laura Q.; Motl, Robert W.; Courneya, Kerry S.

    2010-01-01

    Objective To examine the role of self-efficacy and depression as potential pathways from physical activity to fatigue in two study samples: breast cancer survivors (BCS; N=192) and individuals with multiple sclerosis (MS; N=292). Methods We hypothesized that physical activity would be indirectly associated with fatigue through its influence on self-efficacy and depressive symptomatology. A cross-sectional path analysis (BCS) and a longitudinal panel model (MS) were conducted within a covariance modeling framework. Results Physical activity had a direct effect on self-efficacy, and in turn, self-efficacy had both a direct effect on fatigue and an indirect effect through depressive symptomatology in both samples. In the MS sample, physical activity also had a direct effect on fatigue. All model fit indices were excellent. These associations remained significant when controlling for demographics and health status indicators. Conclusions Our findings suggest support for at least one set of psychosocial pathways from physical activity to fatigue, an important concern in chronic disease. Subsequent work might replicate such associations in other diseased populations and attempt to determine whether model relations change with physical activity interventions, and the extent to which other known correlates of fatigue such as impaired sleep and inflammation can be incorporated into this model. PMID:19949160

  6. Levels and Rates of Physical Activity in Older Adults with Multiple Sclerosis

    PubMed Central

    Klaren, Rachel E.; Sebastiao, Emerson; Chiu, Chung-Yi; Kinnett-Hopkins, Dominique; McAuley, Edward; Motl, Robert W.

    2016-01-01

    There is much evidence supporting the safety and benefits of physical activity in adults with multiple sclerosis (MS) and recent evidence of beneficial effects on physical function in older adults with MS. However, there is very little known about physical activity participation in older adults with conditions such as MS. This study compared levels of physical activity (i.e., sedentary behavior, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA)) and rates of meeting public health guidelines for MVPA (i.e., ≥30 min/day) among young (i.e., ages 20-39 years), middle-aged (i.e., ages 40-59 years) and older adults (i.e., ages ≥60 years) with MS. The sample included 963 persons with MS who provided demographic and clinical information and wore an accelerometer for a 7-day period. The primary analysis involved a between-subjects ANOVA on accelerometer variables (i.e., accelerometer wear time; number of valid days; sedentary behavior in min/day; LPA in min/day; and MVPA in min/day). Collectively, our data indicated that older adults with MS engaged in less MVPA and more sedentary behavior than middle-aged and young adults with MS. Such results highlight the importance of developing physical activity interventions as an effective means for managing the progression and consequences of MS in older adults. PMID:27330842

  7. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    PubMed

    Morrish, F; Isern, N; Sadilek, M; Jeffrey, M; Hockenbery, D M

    2009-07-01

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-(13)C] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by (13)C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased (13)C labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation.

  8. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    SciTech Connect

    Morrish, Fionnuala M.; Isern, Nancy; Sadilek, Martin; Jeffrey, Mark; Hockenbery, David M.

    2009-05-18

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA, and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell cycle entry is unknown. Here, we report the metabolic fates of [U-13C] glucose in serum-stimulated myc-/- and myc+/+ fibroblasts by 13C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased 13C-labeling of ribose sugars, purines, and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked GlcNAc protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing role for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its role in directing metabolic networks required for cell proliferation.

  9. Insights into antioxidant activity of 1-adamantylthiopyridine analogs using multiple linear regression.

    PubMed

    Worachartcheewan, Apilak; Nantasenamat, Chanin; Owasirikul, Wiwat; Monnor, Teerawat; Naruepantawart, Orapan; Janyapaisarn, Sayamon; Prachayasittikul, Supaluk; Prachayasittikul, Virapong

    2014-02-12

    A data set of 1-adamantylthiopyridine analogs (1-19) with antioxidant activity, comprising of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) activities, was used for constructing quantitative structure-activity relationship (QSAR) models. Molecular structures were geometrically optimized at B3LYP/6-31g(d) level and subjected for further molecular descriptor calculation using Dragon software. Multiple linear regression (MLR) was employed for the development of QSAR models using 3 significant descriptors (i.e. Mor29e, F04[N-N] and GATS5v) for predicting the DPPH activity and 2 essential descriptors (i.e. EEig06r and Mor06v) for predicting the SOD activity. Such molecular descriptors accounted for the effects and positions of substituent groups (R) on the 1-adamantylthiopyridine ring. The results showed that high atomic electronegativity of polar substituent group (R = CO2H) afforded high DPPH activity, while substituent with high atomic van der Waals volumes such as R = Br gave high SOD activity. Leave-one-out cross-validation (LOO-CV) and external test set were used for model validation. Correlation coefficient (QCV) and root mean squared error (RMSECV) of the LOO-CV set for predicting DPPH activity were 0.5784 and 8.3440, respectively, while QExt and RMSEExt of external test set corresponded to 0.7353 and 4.2721, respectively. Furthermore, QCV and RMSECV values of the LOO-CV set for predicting SOD activity were 0.7549 and 5.6380, respectively. The QSAR model's equation was then used in predicting the SOD activity of tested compounds and these were subsequently verified experimentally. It was observed that the experimental activity was more potent than the predicted activity. Structure-activity relationships of significant descriptors governing antioxidant activity are also discussed. The QSAR models investigated herein are anticipated to be useful in the rational design and development of novel compounds with antioxidant activity. PMID

  10. Multiple Behavior Change among Church Members Taking Part in the Faith, Activity, and Nutrition Program

    PubMed Central

    Wilcox, Sara

    2013-01-01

    Objective To examine the extent to which participants in a combined physical activity (PA) and dietary intervention achieved changes in multiple health behaviors. Design Group randomized trial; includes participants assigned to the intervention group only. Setting 36 churches in South Carolina. Participants 360 African American church members. Intervention 15-month PA and dietary intervention, guided by the structural ecological model, targeting environmental (i.e. social, cultural, physical) and organizational (i.e. policies, practices) changes within the church. Main Outcome Measures Self-reported PA, fruit and vegetable consumption, fat-, and fiber-related behaviors. Analysis Change in each behavior was defined as unadjusted pretest-posttest improvement ≥0.20 of the baseline standard deviation. The total number and each combination of behaviors changed were calculated. Results 19.2% changed no health behaviors as defined above, 31.4% changed one health behavior, 30.8% changed two health behaviors, 13.3% changed three health behaviors, and 5.3% changed all four of the targeted health behaviors. Combinations of multiple behavior change included PA and dietary behaviors, suggesting both behaviors can be changed simultaneously. Conclusions and Implications Nearly half of participants changed at least two health behaviors. Faith-based interventions targeting environmental and organizational change can successfully change multiple behaviors, potentially leading to greater improvements in public health. PMID:23769297

  11. RHESSI AND TRACE OBSERVATIONS OF MULTIPLE FLARE ACTIVITY IN AR 10656 AND ASSOCIATED FILAMENT ERUPTION

    SciTech Connect

    Joshi, Bhuwan; Kushwaha, Upendra; Cho, K.-S.; Veronig, Astrid M.

    2013-07-01

    We present Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and Transition Region and Coronal Explorer (TRACE) observations of multiple flare activity that occurred in the NOAA active region 10656 over a period of 2 hr on 2004 August 18. Out of four successive flares, three were class C events, and the final event was a major X1.8 solar eruptive flare. The activities during the pre-eruption phase, i.e., before the X1.8 flare, are characterized by three localized episodes of energy release occurring in the vicinity of a filament that produces intense heating along with non-thermal emission. A few minutes before the eruption, the filament undergoes an activation phase during which it slowly rises with a speed of {approx}12 km s{sup -1}. The filament eruption is accompanied by an X1.8 flare, during which multiple hard X-ray (HXR) bursts are observed up to 100-300 keV energies. We observe a bright and elongated coronal structure simultaneously in E(UV) and 50-100 keV HXR images underneath the expanding filament during the period of HXR bursts, which provides strong evidence for ongoing magnetic reconnection. This phase is accompanied by very high plasma temperatures of {approx}31 MK, followed by the detachment of the prominence from the solar source region. From the location, timing, strength, and spectrum of HXR emission, we conclude that the prominence eruption is driven by the distinct events of magnetic reconnection occurring in the current sheet below the erupting prominence. These multi-wavelength observations also suggest that the localized magnetic reconnections associated with different evolutionary stages of the filament in the pre-eruption phase play an important role in destabilizing the active-region filament through the tether-cutting process, leading to large-scale eruption and X-class flare.

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

    PubMed

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

    2015-05-21

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

  13. Chromenopyrazole, a Versatile Cannabinoid Scaffold with in Vivo Activity in a Model of Multiple Sclerosis.

    PubMed

    Morales, Paula; Gómez-Cañas, María; Navarro, Gemma; Hurst, Dow P; Carrillo-Salinas, Francisco J; Lagartera, Laura; Pazos, Ruth; Goya, Pilar; Reggio, Patricia H; Guaza, Carmen; Franco, Rafael; Fernández-Ruiz, Javier; Jagerovic, Nadine

    2016-07-28

    A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies have been performed for some of them. Biological evaluation of the new compounds includes, among others, cannabinoid binding assays, functional studies, and surface plasmon resonance measurements. The most promising compound [43 (PM226)], a selective and potent CB2 agonist isoxazole derivative, was tested in the acute phase of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a well-established animal model of primary progressive multiple sclerosis. Compound 43 dampened neuroinflammation by reducing microglial activation in the TMEV.

  14. Intelligent navigation and multivehicle coordination

    NASA Astrophysics Data System (ADS)

    McKay, Mark D.; Anderson, Matthew O.; Kinoshita, Robert A.; Flann, Nicholas S.

    1999-07-01

    The Idaho National Engineering and Environmental Laboratory (INEEL) and Utah State University's Center for Self-Organizing and Intelligent Systems have developed a team of autonomous robotic vehicles. This paper discusses the development of a strategy that uses a sophisticated, highly intelligent sensor platform to allow centralized coordination between smaller and inexpensive robots. The three components of the multi-agent cooperative scheme are small-scale robots, large-scale robots, and the central control station running a mission and path- planning software. The smaller robots are used for activities where the probability of loss increases, such as Unexploded Ordnance (UXO) or mine detonation. The research is aimed at building simple, inexpensive multi-agent vehicles and an intelligent navigation and multi-vehicle coordination system suitable for UXO, environmental remediation or mine detection. These simplified robots are capable of conducting hunting missions using low-cost positioning sensors and intelligent algorithms. Additionally, a larger sensor-rich intelligent system capable of transporting smaller units to outlying remote sites has been developed. The larger system interfaces to the central control station and provides navigation assistance to multiple low-cost vehicles. Finally, mission and path-planning software serves as the operator control unit, allowing central data collection, map creation and tracking, and an interface to the larger system as well as each smaller unit. The power of this scheme is the ability to scale to the appropriate level for the complexity of the mission.

  15. Ultrasonic waste activated sludge disintegration for recovering multiple nutrients for biofuel production.

    PubMed

    Xie, Guo-Jun; Liu, Bing-Feng; Wang, Qilin; Ding, Jie; Ren, Nan-Qi

    2016-04-15

    Waste activated sludge is a valuable resource containing multiple nutrients, but is currently treated and disposed of as an important source of pollution. In this work, waste activated sludge after ultrasound pretreatment was reused as multiple nutrients for biofuel production. The nutrients trapped in sludge floc were transferred into liquid medium by ultrasonic disintegration during first 30 min, while further increase of pretreatment time only resulted in slight increase of nutrients release. Hydrogen production by Ethanoligenens harbinense B49 from glucose significantly increased with the concentration of ultrasonic sludge, and reached maximum yield of 1.97 mol H2/mol glucose at sludge concentration of 7.75 g volatile suspended solids/l. Without addition of any other chemicals, waste molasses rich in carbohydrate was efficiently turned into hydrogen with yield of 189.34 ml H2/g total sugar by E. harbinense B49 using ultrasonic sludge as nutrients. The results also showed that hydrogen production using pretreated sludge as multiple nutrients was higher than those using standard nutrients. Acetic acid produced by E. harbinense B49 together with the residual nutrients in the liquid medium were further converted into hydrogen (271.36 ml H2/g total sugar) by Rhodopseudomonas faecalis RLD-53 through photo fermentation, while ethanol was the sole end product with yield of 220.26 mg/g total sugar. Thus, pretreated sludge was an efficient nutrients source for biofuel production, which could replace the standard nutrients. This research provided a novel strategy to achieve environmental friendly sludge disposal and simultaneous efficient biofuel recovery from organic waste. PMID:26896823

  16. No association of tobacco use and disease activity in multiple sclerosis

    PubMed Central

    Myhr, Kjell-Morten; Holmøy, Trygve; Benth, Jūratė Šaltytė; Løken-Amsrud, Kristin I.; Wergeland, Stig; Beiske, Antonie G.; Bjerve, Kristian S.; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Bakke, Søren J.; Torkildsen, Øivind

    2016-01-01

    Objective: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). Methods: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. Results: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non–tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. Conclusion: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms. PMID:27458599

  17. Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life.

    PubMed

    Stevenson, Andrew; Burkhardt, Jürgen; Cockell, Charles S; Cray, Jonathan A; Dijksterhuis, Jan; Fox-Powell, Mark; Kee, Terence P; Kminek, Gerhard; McGenity, Terry J; Timmis, Kenneth N; Timson, David J; Voytek, Mary A; Westall, Frances; Yakimov, Michail M; Hallsworth, John E

    2015-02-01

    Since a key requirement of known life forms is available water (water activity; aw ), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earth's present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth.

  18. Discovery of HDAC Inhibitors with Potent Activity Against Multiple Malaria Parasite Life Cycle Stages

    PubMed Central

    Hansen, Finn K.; Sumanadasa, Subathdrage D. M.; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U.; Winzeler, Elizabeth A.; Avery, Vicky M.; Andrews, Katherine T.; Kurz, Thomas

    2015-01-01

    In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage P. falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against P. berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. PMID:24904967

  19. Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life.

    PubMed

    Stevenson, Andrew; Burkhardt, Jürgen; Cockell, Charles S; Cray, Jonathan A; Dijksterhuis, Jan; Fox-Powell, Mark; Kee, Terence P; Kminek, Gerhard; McGenity, Terry J; Timmis, Kenneth N; Timson, David J; Voytek, Mary A; Westall, Frances; Yakimov, Michail M; Hallsworth, John E

    2015-02-01

    Since a key requirement of known life forms is available water (water activity; aw ), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earth's present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth. PMID:25142751

  20. Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer

    PubMed Central

    Stoyanova, Tanya; Riedinger, Mireille; Lin, Shu; Faltermeier, Claire M.; Smith, Bryan A.; Zhang, Kelvin X.; Going, Catherine C.; Goldstein, Andrew S.; Lee, John K.; Drake, Justin M.; Rice, Meghan A.; Hsu, En-Chi; Nowroozizadeh, Behdokht; Castor, Brandon; Orellana, Sandra Y.; Blum, Steven M.; Cheng, Donghui; Pienta, Kenneth J.; Reiter, Robert E.; Pitteri, Sharon J.; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer. PMID:27694579

  1. The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.

    PubMed

    Gunn, Ellen J; Williams, John T; Huynh, Daniel T; Iannotti, Michael J; Han, Changho; Barrios, Francis J; Kendall, Stephen; Glackin, Carlotta A; Colby, David A; Kirshner, Julia

    2011-06-01

    Multiple myeloma (MM) is an incurable plasma cell malignancy where nearly all patients succumb to a relapse. The current preclinical models of MM target the plasma cells, constituting the bulk of the tumor, leaving the cancer stem cells to trigger a relapse. Utilizing a three-dimensional tissue culture system where cells were grown in extracellular matrix designed to reconstruct human bone marrow, we tested the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product inhibitors of nuclear factor κB (NFκB). Here we show that parthenolide and andrographolide are potent anti-MM-CSC agents. Both natural products demonstrated preferential toxicity toward MM-CSCs over non-tumorigenic MM cells. Addition of the bone marrow stromal compartment abrogated andrographolide activity while having no effect on parthenolide cytoxicity. This is the first report of a natural product with anti-CSC activity in myeloma, suggesting that it has the potential to improve the survival of patients with MM by eliminating the relapse-causing MM-CSCs. PMID:21417826

  2. Exploring Physical Activity Behaviour of Persons with Multiple Sclerosis: A Qualitative Pilot Study

    PubMed Central

    Resnik, Linda; Allen, Susan

    2015-01-01

    Purpose Identify facilitators and barriers to physical activity (PA), and explore the utility of Social Cognitive Theory (SCT) and Transactional Model of Stress and Coping (TMSC) in understanding PA behaviour among persons with multiple sclerosis (MS). Methods Thirteen participants from a clinical trial were interviewed and classified as physically active, sometimes active, or inactive based on the Health-Promoting Lifestyle Profile-II. Interviews were analysed using analytical induction, which consisted of coding data into pre-established categories and then exploring similarities and differences between groups. Pre-established coding categories were constructs from SCT (i.e. environment, expectations, self-efficacy, and self-regulation) and TMSC (i.e. stress appraisal and coping style). Results Inactive and active participants differed in their self-regulation skills, self-efficacy, and coping styles. Common barriers to PA included symptoms and the physical and social environment. Facilitators of PA included strong self-regulation skills, confidence to overcome symptoms to engage in PA (i.e. barrier self-efficacy), and positive coping styles. Conclusion Results from this pilot study suggest that PA interventions will need to implement multiple strategies that target self-efficacy, social environment, and coping styles. We found SCT and TMSC useful in understanding PA behaviour among persons with MS; however, a limitation to these theories is that they are not explicit in the relationship between health and cognitions. Future research will need to explore how to incorporate models of health and function into existing behaviour change theories. PMID:19479491

  3. Understanding walking activity in multiple sclerosis: step count, walking intensity and uninterrupted walking activity duration related to degree of disability.

    PubMed

    Neven, An; Vanderstraeten, Annelien; Janssens, Davy; Wets, Geert; Feys, Peter

    2016-09-01

    In multiple sclerosis (MS), physical activity (PA) is most commonly measured as number of steps, while also walking intensity and walking activity duration are keys for a healthy lifestyle. The aim of this study was to investigate (1) the number of steps persons with MS (PwMS) take; (2) the number of steps they take at low and moderate intensity; and (3) their walking activity duration for 2, 3, 6, 10, 12 and 14 uninterrupted minutes; all related to the degree of disability. 64 PwMS participated, distinguished in a mild (n = 31) and moderate MS subgroup (n = 34) based on their ambulatory dysfunction (Disease Steps). Standardized clinical tests were performed, and step data from the StepWatch Activity Monitor were collected for seven consecutive days. The results showed that (1) step count in PwMS was lower than PA recommendations, and is negatively influenced by a higher disability degree. (2) No walking was registered during 77 % of the day. PwMS are making steps for 22 % at low and only 1 % at moderate intensity. (3) Both MS subgroups rarely walk for more than six uninterrupted minutes, especially not at moderate intensity. PwMS need to be encouraged to make steps at moderate intensity, and to make steps for longer periods of time (minimal ten uninterrupted minutes).

  4. Bridged bis(beta-cyclodextrin)s possessing coordinated metal center(s) and their inclusion complexation behavior with model substrates: enhanced molecular binding ability by multiple recognition.

    PubMed

    Liu, Y; Chen, Y; Li, L; Zhang, H Y; Liu, S X; Guan, X D

    2001-12-14

    To investigate quantitatively the cooperative binding ability of several beta-cyclodextrin oligomers bearing single or multiligated metal center(s), the inclusion complexation behavior of four bis(beta-cyclodextrin)s (2-5) linked by 2,2'-bipyridine-4,4'-dicarboxy tethers and their copper(II) complexes (6-9) with representative dye guests, i.e., methyl orange (MO), acridine red (AR), rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonic acid (ANS), and sodium 6-(p-toludino)-2-naphthalenesulfonate (TNS), have been examined in aqueous solution at 25 degrees C by means of UV-vis, circular dichroism, fluorescence, and 2D NMR spectroscopy. The results obtained indicate that bis(beta-cyclodextrin)s 2-5 can associate with one or three copper(II) ion(s) producing 2:1 or 2:3 bis(beta-cyclodextrin)-copper(II) complexes. These metal-ligated oligo(beta-cyclodextrin)s can bind two model substrates to form intramolecular 2:2 host-guest inclusion complexes and thus significantly enhance the original binding abilities of parent beta-cyclodextrin and bis(beta-cyclodextrin) toward model substrates through the cooperative binding of two guest molecules by four tethered cyclodextrin moieties, as well as the additional binding effect supplied by ligated metal center(s). Host 6 showed the highest enhancement of the stability constant, up to 38.3 times for ANS as compared with parent beta-cyclodextrin. The molecular binding mode and stability constant of substrates by bridged bis- and oligo(beta-cyclodextrin)s 2-9 are discussed from the viewpoint of the size/shape-fit interaction and molecular multiple recognition between host and guest.

  5. Keep meaning in conversational coordination

    PubMed Central

    Cuffari, Elena C.

    2014-01-01

    Coordination is a widely employed term across recent quantitative and qualitative approaches to intersubjectivity, particularly approaches that give embodiment and enaction central explanatory roles. With a focus on linguistic and bodily coordination in conversational contexts, I review the operational meaning of coordination in recent empirical research and related theorizing of embodied intersubjectivity. This discussion articulates what must be involved in treating linguistic meaning as dynamic processes of coordination. The coordination approach presents languaging as a set of dynamic self-organizing processes and actions on multiple timescales and across multiple modalities that come about and work in certain domains (those jointly constructed in social, interactive, high-order sense-making). These processes go beyond meaning at the level that is available to first-person experience. I take one crucial consequence of this to be the ubiquitously moral nature of languaging with others. Languaging coordinates experience, among other levels of behavior and event. Ethical effort is called for by the automatic autonomy-influencing forces of languaging as coordination. PMID:25520693

  6. Effects of an aqueous extract of Orbignya phalerata Mart on locomotor activity and motor coordination in mice and as antioxidant in vitro.

    PubMed

    Silva, A P dos S; Cerqueira, G S; Nunes, L C C; de Freitas, R M

    2012-03-01

    The antioxidant activities of aqueous extract (AE) of Orbignya phalerata were assessed in vitro as well as its effect on locomotor activity and motor coordination in mice. AE does not possesses a strong antioxidant potential according to the scavenging assays; it also did not present scavenger activity in vitro. Following oral administration, AE (1, 2 and 3 g/kg) did not significantly change the motor activity of animals when compared with the control group, up to 24 h after administration and did not alter the remaining time of the animals on the Rota-rod apparatus. Further studies currently in progress will enable us to understand the mechanisms of action of the aqueous extract of Orbignya phalerata widely used in Brazilian flok medicine.

  7. Multiple implantation and multiple annealing of phosphorus doped germanium to achieve n-type activation near the theoretical limit

    NASA Astrophysics Data System (ADS)

    Kim, Jeehwan; Bedell, Stephen W.; Sadana, Devendra K.

    2012-09-01

    Full activation of n-type dopant in germanium (Ge) reaching to its solid solubility has never been achieved by using ion implantation doping technique. This is because implantation of dopants always leaves defects such as vacancy and interstitials in the Ge crystal. While implantation-induced defects are electrically neutral for the most of semiconductor materials, they are electrically positive for Ge resulting in compensation of n-type dopants. In this Letter, we verified that 5 × 1019 P/cm3 is the maximum active concentration, which can be fully activated in germanium "without leaving implantation damage" per implantation/annealing cycle. The repetition of implantation and annealing of phosphorous (P) with the concentration of 5 × 1019 cm-3 leads to the activation of 1 × 1020 P/cm3 close to its solid solubility limit of 2 × 1020 P/cm3.

  8. Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways

    PubMed Central

    Doyle, Alexander; Zhang, Guohua; Abdel Fattah, Elmoataz A.; Eissa, N. Tony; Li, Yi-Ping

    2011-01-01

    Cachectic muscle wasting is a frequent complication of many inflammatory conditions, due primarily to excessive muscle catabolism. However, the pathogenesis and intervention strategies against it remain to be established. Here, we tested the hypothesis that Toll-like receptor 4 (TLR4) is a master regulator of inflammatory muscle catabolism. We demonstrate that TLR4 activation by lipopolysaccharide (LPS) induces C2C12 myotube atrophy via up-regulating autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx and MuRF1. TLR4-mediated activation of p38 MAPK is necessary and sufficient for the up-regulation of atrogin1/MAFbx and autophagosomes, resulting in myotube atrophy. Similarly, LPS up-regulates muscle autophagosome formation and ubiquitin ligase expression in mice. Importantly, autophagy inhibitor 3-methyladenine completely abolishes LPS-induced muscle proteolysis, while proteasome inhibitor lactacystin partially blocks it. Furthermore, TLR4 knockout or p38 MAPK inhibition abolishes LPS-induced muscle proteolysis. Thus, TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways.—Doyle, A., Zhang, G., Abdel Fattah, E. A., Eissa, N. T., Li, Y.-P. Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways. PMID:20826541

  9. Novel Ni(II) and Zn(II) complexes coordinated by 2-arylaminomethyl-1H-benzimidazole: Molecular structures, spectral, DFT studies and evaluation of biological activity

    NASA Astrophysics Data System (ADS)

    Abdel-Ghani, Nour T.; Abo El-Ghar, Maha F.; Mansour, Ahmed M.

    2013-03-01

    [NiL1,2Cl2(OH2)3]·zH2O and [ZnL1,2(CH3CO2)2] (L1 = (1H-benzimidazol-2-ylmethyl)-N-phenyl amine, z = 0 and L2 = 2-[(1H-Benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester, z = 1) complexes have been synthesized and characterized by a variety of physico-chemical techniques. The central Ni(II) ion is coordinated by only the pyridine-type nitrogen (Npy) of benzimidazole ring, three water molecules and two chlorido ligands forming a distorted octahedral geometry. Five coordinated zinc complexes were obtained, where the coordination sphere of zinc ion is made up of secondary amino group (NHsec), Npy and two acetate groups, one acts as a unidentate and the other as a bidentate. A theoretical DFT/UB3LYP method combined with LANL2DZ basis set shows that all the metal-ligand bonds are of the L → M type. Electronic structures have been calculated using TD-DFT method. The antibacterial activity of NiL2 complexes decreases by the introduction of COOCH3 group in the ortho-position of the aniline moiety.

  10. Vision guided automatic measuring in coordinate metrology

    NASA Astrophysics Data System (ADS)

    Qin, Yuhong; Wang, Lei; Xie, Lusheng; Huang, Yuanqing

    2008-12-01

    A novel automatically measuring planning method in coordinate metrology based on computer vision is presented in this paper. An active stereo vision system is established by attaching a CCD camera to the mechanical probe of the coordinate measuring machine (CMM). Through the movement of the probe of the CMM, as well as the camera, 3D edge characters of the object can be acquired, which are used as clues for automatically coordinate measuring. A multi-baseline matching method is presented to overcome the ambiguity in stereo matching, and a quadratic interpolating is used in sub pixel matching to get continuous depth image. The matching is only done on character edges in images, so it is much faster and more robust. Two methods of measuring path planning are put forward, in one way, a 2D characteristic edge image which are often stand for rapidly changes in depth or curvature of object surface can be acquired by projecting 3D edge characters to a scanning plane, and then the sampling points of mechanical probe are selected depending on the edge image. In the other way, surface patches are fitted to these 3D edges, and the sampling grid is determined by the type and area of every patch. Using these techniques, a highly automated high-speed, high-precision, 3-D coordinate acquisition system based on multiple-sensor integration can be developed. It has potential applications in manufacturing problems as metrology, inspection, and reverse engineering.

  11. Multiple signals modulate the activity of the complex sensor kinase TodS

    PubMed Central

    Silva-Jiménez, Hortencia; Ortega, Álvaro; García-Fontana, Cristina; Ramos, Juan Luis; Krell, Tino

    2015-01-01

    The reason for the existence of complex sensor kinases is little understood but thought to lie in the capacity to respond to multiple signals. The complex, seven-domain sensor kinase TodS controls in concert with the TodT response regulator the expression of the toluene dioxygenase pathway in Pseudomonas putida F1 and DOT-T1E. We have previously shown that some aromatic hydrocarbons stimulate TodS activity whereas others behave as antagonists. We show here that TodS responds in addition to the oxidative agent menadione. Menadione but no other oxidative agent tested inhibited TodS activity in vitro and reduced PtodX expression in vivo. The menadione signal is incorporated by a cysteine-dependent mechanism. The mutation of the sole conserved cysteine of TodS (C320) rendered the protein insensitive to menadione. We evaluated the mutual opposing effects of toluene and menadione on TodS autophosphorylation. In the presence of toluene, menadione reduced TodS activity whereas toluene did not stimulate activity in the presence of menadione. It was shown by others that menadione increases expression of glucose metabolism genes. The opposing effects of menadione on glucose and toluene metabolism may be partially responsible for the interwoven regulation of both catabolic pathways. This work provides mechanistic detail on how complex sensor kinases integrate different types of signal molecules. PMID:24986263

  12. Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees.

    PubMed

    Lauw, F N; Dekkers, P E; te Velde, A A; Speelman, P; Levi, M; Kurimoto, M; Hack, C E; van Deventer, S J; van der Poll, T

    1999-03-01

    To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.

  13. Activated caspase-9 immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy.

    PubMed

    Kawamoto, Yasuhiro; Ayaki, Takashi; Urushitani, Makoto; Ito, Hidefumi; Takahashi, Ryosuke

    2016-08-15

    The mitochondria play an important role in apoptotic cell death, and the released cytochrome c from the mitochondria promotes the formation of the apoptosome, which contains cytochrome c, Apaf-1 and caspase-9, resulting in the activation of caspase-9 and the promotion of the apoptotic cascade. To investigate the role of mitochondria-dependent apoptotic cell death in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on apoptosome-related proteins in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. We then performed double-labeling immunohistochemistry for activated caspase-9 and α-synuclein in some sections from 10 patients with MSA. In the brains with MSA, glial cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were intensely immunoreactive for cytochrome c, Apaf-1 and caspase-9. Activated caspase-9 immunoreactivities were also confirmed to be densely localized to both GCIs and NCIs using two types of anti-cleaved caspase-9 antibodies. The semiquantitative analyses using the upper pontine sections double-immunostained with cleaved caspase-9 and α-synuclein demonstrated that approximately 80% of GCIs and NCIs were immunopositive for cleaved caspase-9. Our results suggest that the formation of the apoptosome accompanied by the activation of caspase-9 may occur in brains affected by MSA, and that a mitochondria-dependent apoptotic pathway may be partially associated with the pathogenesis of MSA. PMID:27345387

  14. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis

    PubMed Central

    Thell, Kathrin; Hellinger, Roland; Sahin, Emine; Michenthaler, Paul; Gold-Binder, Markus; Haider, Thomas; Kuttke, Mario; Liutkevičiūtė, Zita; Göransson, Ulf; Gründemann, Carsten; Schabbauer, Gernot; Gruber, Christian W.

    2016-01-01

    Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2–dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders. PMID:27035952

  15. TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints

    PubMed Central

    Guo, Xiaoyun; Yin, Haifeng; Chen, Yi; Li, Lei; Li, Jing; Liu, Qinghang

    2016-01-01

    Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, although the underlying molecular regulatory mechanisms are not well defined. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8-mediated apoptotic signaling through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced cell death through the induction of RIP1 phosphorylation/activation and necrosome formation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role for the adaptor protein TNF receptor-associated protein with death domain (TRADD) in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key pro-survival signaling proteins and necrosome formation. Thus, we identified new regulatory mechanisms underlying the critical role of TAK1 in cell survival through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis. PMID:27685625

  16. An application of the active time model to multiple concurrent variable-interval schedules.

    PubMed

    Brown, Emily Kathryn; Cleaveland, J Mark

    2009-06-01

    The current experiment investigates whether an active time model can account for anomalous results that have emerged from multiple schedule, concurrent variable-interval (VI) VI experiments. The model assumes that (1) during concurrent VI VI training pigeons learn a function that relates time since the most immediate response, i.e., active time, to changeover probabilities and (2) that molar preference is the result of an interaction between inter-response time frequencies and the learned active time changeover functions. Pigeons were trained under a concurrent VI 30-s VI 30-s schedule and a concurrent VI 60-s VI 60-s schedule. Probes were conducted in which VI 30-s and VI 60-s stimuli were paired. During these probes, birds allocated choices equally to the stimuli. The active time model accurately fit individual subject data. In contrast data were not fit by a variant of scalar expectancy theory proposed by Gibbon [Gibbon, J., 1995. Dynamics of time matching: arousal makes better seem worse. Psychon. Bull. Rev. 2, 208-215].

  17. A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses.

    PubMed

    Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

    2016-01-01

    A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

  18. A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

    PubMed Central

    Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

    2016-01-01

    A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

  19. Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis.

    PubMed

    Howell, Owain W; Rundle, Jon L; Garg, Anurag; Komada, Masayuki; Brophy, Peter J; Reynolds, Richard

    2010-10-01

    The complex manifestations of chronic multiple sclerosis (MS)are due in part to widespread axonal abnormalities that affect lesional and nonlesional areas in the central nervous system. We describe an association between microglial activation and axon/oligodendrocyte pathology at nodal and paranodal domains in normal-appearing white matter (NAWM) of MS cases and in experimental autoimmune encephalomyelitis (EAE). The extent of paranodal axoglial (neurofascin-155(+)/Caspr1(+)) disruption correlated with local microglial inflammation and axonal injury (expression of nonphosphorylated neurofilaments) in MS NAWM. These changes were independent of demyelinating lesions and did not correlate with the density of infiltrating lymphocytes. Similar axoglial alterations were seen in the subcortical white matter of Parkinson disease cases and in preclinical EAE, at a time point when there is microglial activation before the infiltration of immune cells. Disruption of the axoglial unit in adjuvant-immunized animals was reversible and coincided with the resolution of microglial inflammation; paranodal damage and microglial inflammation persisted in chronic EAE. Axoglial integrity could be preserved by the administration of minocycline, which inhibited microglial activation, in actively immunized animals. These data indicate that, in MS NAWM, permanent disruption to axoglial domains in an environment of microglial inflammation is an early indicator of axonal injury that likely affects nerve conduction and may contribute to physiologic dysfunction.

  20. Tyrosine kinase BMX phosphorylates phosphotyrosine-primed motif mediating the activation of multiple receptor tyrosine kinases.

    PubMed

    Chen, Sen; Jiang, Xinnong; Gewinner, Christina A; Asara, John M; Simon, Nicholas I; Cai, Changmeng; Cantley, Lewis C; Balk, Steven P

    2013-05-28

    The nonreceptor tyrosine kinase BMX (bone marrow tyrosine kinase gene on chromosome X) is abundant in various cell types and activated downstream of phosphatidylinositol-3 kinase (PI3K) and the kinase Src, but its substrates are unknown. Positional scanning peptide library screening revealed a marked preference for a priming phosphorylated tyrosine (pY) in the -1 position, indicating that BMX substrates may include multiple tyrosine kinases that are fully activated by pYpY sites in the kinase domain. BMX phosphorylated focal adhesion kinase (FAK) at Tyr⁵⁷⁷ subsequent to its Src-mediated phosphorylation at Tyr⁵⁷⁶. Loss of BMX by RNA interference or by genetic deletion in mouse embryonic fibroblasts (MEFs) markedly impaired FAK activity. Phosphorylation of the insulin receptor in the kinase domain at Tyr¹¹⁸⁹ and Tyr¹¹⁹⁰, as well as Tyr¹¹⁸⁵, and downstream phosphorylation of the kinase AKT at Thr³⁰⁸ were similarly impaired by BMX deficiency. However, insulin-induced phosphorylation of AKT at Ser⁴⁷³ was not impaired in Bmx knockout MEFs or liver tissue from Bmx knockout mice, which also showed increased insulin-stimulated glucose uptake, possibly because of decreased abundance of the phosphatase PHLPP (PH domain leucine-rich repeat protein phosphatase). Thus, by identifying the pYpY motif as a substrate for BMX, our findings suggest that BMX functions as a central regulator among multiple signaling pathways mediated by tyrosine kinases. PMID:23716717