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Sample records for activation coordinates multiple

  1. Imaging the coordination of multiple signaling activities in living cells

    PubMed Central

    Welch, Christopher M.; Elliott, Hunter; Danuser, Gaudenz; Hahn, Klaus M.

    2013-01-01

    Preface Cellular signal transduction occurs in complex and redundant interaction networks that are best examined at the level of single cells by simultaneously monitoring the activation dynamics of multiple components. Recent advances in biosensor technology have made it possible to visualize and quantify the activation of multiple network nodes in the same living cell. The precision and scope of this approach has been greatly extended by novel computational approaches to determine the relationships between different networks, studied in separate cells. PMID:22016058

  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. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Optimizing plasmonic nanoantennas via coordinated multiple coupling

    NASA Astrophysics Data System (ADS)

    Lin, Linhan; Zheng, Yuebing

    2015-10-01

    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.

  9. Optimizing plasmonic nanoantennas via coordinated multiple coupling.

    PubMed

    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

  10. 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.

  11. Neuromuscular synaptogenesis: coordinating partners with multiple functions.

    PubMed

    Darabid, Houssam; Perez-Gonzalez, Anna P; Robitaille, Richard

    2014-11-01

    The formation of highly efficient and reliable synapses at the neuromuscular junction (NMJ) relies on dynamic molecular interactions. Studies of the development and maturation of the NMJ have focused on events that are dependent on synaptic activity and that require the coordinated actions of nerve- and muscle-derived molecules with different targets and effects. More recently, perisynaptic Schwann cells--the glial cells at NMJs--have become an important focus of research. These glia concomitantly contribute to pre- and postsynaptic maturation while undergoing maturation themselves. Thus, an intricate 'danse à trois’'regulates the maturation of the NMJ to form a highly efficient communication unit, in which fine glial processes lie in close proximity to a highly concentrated population of postsynaptic receptors and perfectly aligned presynaptic release sites. PMID:25493308

  12. 20 CFR 631.37 - Coordination activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Coordination activities. 631.37 Section 631... TITLE III OF THE JOB TRAINING PARTNERSHIP ACT State Administration § 631.37 Coordination activities. (a... U.S.C. 2311) or part 617 of this chapter (section 311(b)(10)). Such coordination shall be...

  13. 20 CFR 631.37 - Coordination activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Coordination activities. 631.37 Section 631... TITLE III OF THE JOB TRAINING PARTNERSHIP ACT State Administration § 631.37 Coordination activities. (a... U.S.C. 2311) or part 617 of this chapter (section 311(b)(10)). Such coordination shall be...

  14. [General coordination of hospital activity].

    PubMed

    Rodríguez, Paz; Serra, José Antonio

    2005-03-01

    The present article describes the organizational and general coordination measures taken by the hospital management to attend the 325 victims who arrived at our hospital after the terrorist attack on the morning of 11 March. Firstly, we summarize the activity performed by the extra-hospital emergency services and the distribution of the victims in centers. Secondly, we describe in greater detail the interventions performed to initiate the External Emergency Action Plan in our hospital, the triage system and identification of patients who used it, as well as the resources in terms of beds, operating rooms and personnel that were used on that day. Lastly, by way of discussion, we provide a critical analysis of our interventions. PMID:15771833

  15. 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…

  16. 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

  17. Coordinating Multiple Spacecraft Assets for Joint Science Campaigns

    NASA Technical Reports Server (NTRS)

    Estlin, Tara; Chien, Steve; Castano, Rebecca; Gaines, Daniel; de Granville, Charles; Doubleday, Josh; Anderson, Robert C.; Knight, Russell; Bornstein, Benjamin; Rabideau, Gregg; Tang, Benyang

    2010-01-01

    This paper describes technology to support a new paradigm of space science campaigns. These campaigns enable opportunistic science observations to be autonomously coordinated between multiple spacecraft. Coordinated spacecraft can consist of multiple orbiters, landers, rovers, or other in-situ vehicles (such as an aerobot). In this paradigm, opportunistic science detections can be cued by any of these assets where additional spacecraft are requested to take further observations characterizing the identified event or surface feature. Such coordination will enable a number of science campaigns not possible with present spacecraft technology. Examples from Mars include enabling rapid data collection from multiple craft on dynamic events such as new Mars dark slope streaks, dust-devils or trace gases. Technology to support the identification of opportunistic science events and/or the re-tasking of a spacecraft to take new measurements of the event is already in place on several individual missions such as the Mars Exploration Rover (MER) Mission and the Earth Observing One (EO1) Mission. This technology includes onboard data analysis techniques as well as capabilities for planning and scheduling. This paper describes how these techniques can be cue and coordinate multiple spacecraft in observing the same science event from their different vantage points.

  18. ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth.

    PubMed

    Atanassov, Boyko S; Mohan, Ryan D; Lan, Xianjiang; Kuang, Xianghong; Lu, Yue; Lin, Kevin; McIvor, Elizabeth; Li, Wenqian; Zhang, Ying; Florens, Laurence; Byrum, Stephanie D; Mackintosh, Samuel G; Calhoun-Davis, Tammy; Koutelou, Evangelia; Wang, Li; Tang, Dean G; Tackett, Alan J; Washburn, Michael P; Workman, Jerry L; Dent, Sharon Y R

    2016-05-19

    Histone H2B monoubiquitination (H2Bub1) is centrally involved in gene regulation. The deubiquitination module (DUBm) of the SAGA complex is a major regulator of global H2Bub1 levels, and components of this DUBm are linked to both neurodegenerative diseases and cancer. Unexpectedly, we find that ablation of USP22, the enzymatic center of the DUBm, leads to a reduction, rather than an increase, in global H2bub1 levels. In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity. Like USP22, USP51 and USP27X are required for normal cell proliferation, and their depletion suppresses tumor growth. Our results reveal that ATXN7L3 and ENY2 orchestrate activities of multiple deubiquitinating enzymes and that imbalances in these activities likely potentiate human diseases including cancer. PMID:27132940

  19. Economical production and transshipment policy for coordinating multiple production sites

    NASA Astrophysics Data System (ADS)

    Kim, Taebok; Goyal, Suresh Kumar

    2012-05-01

    In this article, we study the coordination mechanism dealing with a production-transshipment policy across the multiple regions supplying multiple products. It is assumed that each production site has its own dedicated demand region consuming multiple products. The main concern is how to determine both the production quantity and the lot-apportioning policy while minimising the relevant supply chain cost. This decision issue is formulated as a non-linear mathematical model to determine several relevant decision variables. We propose the solution procedure for deriving the production-transshipment policy minimising the overall supply chain cost.

  20. Multiple measurement models of articulated arm coordinate measuring machines

    NASA Astrophysics Data System (ADS)

    Zheng, Dateng; Xiao, Zhongyue; Xia, Xiang

    2015-09-01

    The existing articulated arm coordinate measuring machines(AACMM) with one measurement model are easy to cause low measurement accuracy because the whole sampling space is much bigger than the result in the unstable calibration parameters. To compensate for the deficiency of one measurement model, the multiple measurement models are built by the Denavit-Hartenberg's notation, the homemade standard rod components are used as a calibration tool and the Levenberg-Marquardt calibration algorithm is applied to solve the structural parameters in the measurement models. During the tests of multiple measurement models, the sample areas are selected in two situations. It is found that the measurement errors' sigma value(0.083 4 mm) dealt with one measurement model is nearly two times larger than that of the multiple measurement models(0.043 1 mm) in the same sample area. While in the different sample area, the measurement errors' sigma value(0.054 0 mm) dealt with the multiple measurement models is about 40% of one measurement model(0.137 3 mm). The preliminary results suggest that the measurement accuracy of AACMM dealt with multiple measurement models is superior to the accuracy of the existing machine with one measurement model. This paper proposes the multiple measurement models to improve the measurement accuracy of AACMM without increasing any hardware cost.

  1. 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.

  2. Activity Coordinators: The View from the Bottom

    ERIC Educational Resources Information Center

    Bucci, Frank A.

    1971-01-01

    Data for this study was drawn for an extensive study on personnel practices. This particular report focuses on the position of coordinator of student activities which is seen as ranking low on the totem pole in regard to benefits, perceived responsibilities, and perception by other staff personnel. (CJ)

  3. 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.

  4. 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.

  5. 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

  6. Abstract-Reasoning Software for Coordinating Multiple Agents

    NASA Technical Reports Server (NTRS)

    Clement, Bradley; Barrett, Anthony; Rabideau, Gregg; Knight, Russell

    2003-01-01

    A computer program for scheduling the activities of multiple agents that share limited resources has been incorporated into the Automated Scheduling and Planning Environment (ASPEN) software system, aspects of which have been reported in several previous NASA Tech Briefs articles. In the original intended application, the agents would be multiple spacecraft and/or robotic vehicles engaged in scientific exploration of distant planets. The program could also be used on Earth in such diverse settings as production lines and military maneuvers. This program includes a planning/scheduling subprogram of the iterative repair type that reasons about the activities of multiple agents at abstract levels in order to greatly improve the scheduling of their use of shared resources. The program summarizes the information about the constraints on, and resource requirements of, abstract activities on the basis of the constraints and requirements that pertain to their potential refinements (decomposition into less-abstract and ultimately to primitive activities). The advantage of reasoning about summary information is that time needed to find consistent schedules is exponentially smaller than the time that would be needed for reasoning about the same tasks at the primitive level.

  7. 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

  8. Interactive coordinated multiple-view visualization of biomechanical motion data.

    PubMed

    Keefe, Daniel F; Ewert, Marcus; Ribarsky, William; Chang, Remco

    2009-01-01

    We present an interactive framework for exploring space-time and form-function relationships in experimentally collected high-resolution biomechanical data sets. These data describe complex 3D motions (e.g. chewing, walking, flying) performed by animals and humans and captured via high-speed imaging technologies, such as biplane fluoroscopy. In analyzing these 3D biomechanical motions, interactive 3D visualizations are important, in particular, for supporting spatial analysis. However, as researchers in information visualization have pointed out, 2D visualizations can also be effective tools for multi-dimensional data analysis, especially for identifying trends over time. Our approach, therefore, combines techniques from both 3D and 2D visualizations. Specifically, it utilizes a multi-view visualization strategy including a small multiples view of motion sequences, a parallel coordinates view, and detailed 3D inspection views. The resulting framework follows an overview first, zoom and filter, then details-on-demand style of analysis, and it explicitly targets a limitation of current tools, namely, supporting analysis and comparison at the level of a collection of motions rather than sequential analysis of a single or small number of motions. Scientific motion collections appropriate for this style of analysis exist in clinical work in orthopedics and physical rehabilitation, in the study of functional morphology within evolutionary biology, and in other contexts. An application is described based on a collaboration with evolutionary biologists studying the mechanics of chewing motions in pigs. Interactive exploration of data describing a collection of more than one hundred experimentally captured pig chewing cycles is described. PMID:19834212

  9. 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

  10. Drawing from memory: hand-eye coordination at multiple scales.

    PubMed

    Huette, Stephanie; Kello, Christopher T; Rhodes, Theo; Spivey, Michael J

    2013-01-01

    Eyes move to gather visual information for the purpose of guiding behavior. This guidance takes the form of perceptual-motor interactions on short timescales for behaviors like locomotion and hand-eye coordination. More complex behaviors require perceptual-motor interactions on longer timescales mediated by memory, such as navigation, or designing and building artifacts. In the present study, the task of sketching images of natural scenes from memory was used to examine and compare perceptual-motor interactions on shorter and longer timescales. Eye and pen trajectories were found to be coordinated in time on shorter timescales during drawing, and also on longer timescales spanning study and drawing periods. The latter type of coordination was found by developing a purely spatial analysis that yielded measures of similarity between images, eye trajectories, and pen trajectories. These results challenge the notion that coordination only unfolds on short timescales. Rather, the task of drawing from memory evokes perceptual-motor encodings of visual images that preserve coarse-grained spatial information over relatively long timescales as well. PMID:23554894

  11. Drawing from Memory: Hand-Eye Coordination at Multiple Scales

    PubMed Central

    Spivey, Michael J.

    2013-01-01

    Eyes move to gather visual information for the purpose of guiding behavior. This guidance takes the form of perceptual-motor interactions on short timescales for behaviors like locomotion and hand-eye coordination. More complex behaviors require perceptual-motor interactions on longer timescales mediated by memory, such as navigation, or designing and building artifacts. In the present study, the task of sketching images of natural scenes from memory was used to examine and compare perceptual-motor interactions on shorter and longer timescales. Eye and pen trajectories were found to be coordinated in time on shorter timescales during drawing, and also on longer timescales spanning study and drawing periods. The latter type of coordination was found by developing a purely spatial analysis that yielded measures of similarity between images, eye trajectories, and pen trajectories. These results challenge the notion that coordination only unfolds on short timescales. Rather, the task of drawing from memory evokes perceptual-motor encodings of visual images that preserve coarse-grained spatial information over relatively long timescales as well. PMID:23554894

  12. 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 activities. (a) Each State with a delegation of authority shall submit annually to the MMS an audit...

  13. 30 CFR 1229.122 - Coordination of audit activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... scheduled for audit. This workplan must be submitted 120 days prior to the beginning of each fiscal year. A... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Coordination of audit activities. 1229.122....122 Coordination of audit activities. (a) Each State with a delegation of authority shall...

  14. 23 CFR 450.208 - Coordination of planning process activities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Coordination of planning process activities. 450.208 Section 450.208 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PLANNING AND RESEARCH PLANNING ASSISTANCE AND STANDARDS Statewide Transportation Planning and Programming § 450.208 Coordination of planning process activities. (a)...

  15. 42 CFR 476.104 - Coordination of activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Coordination of activities. 476.104 Section 476.104 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 476.104 Coordination of activities. In order to achieve efficient and economical review, a QIO...

  16. 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...

  17. 34 CFR 75.580 - Coordination with other activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 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...

  18. 34 CFR 75.580 - Coordination with other activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 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. 34 CFR 75.580 - Coordination with other activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 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...

  20. 34 CFR 75.580 - Coordination with other activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 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...

  1. 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.

  2. 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…

  3. Coordinate-targeted fluorescence nanoscopy with multiple off states

    NASA Astrophysics Data System (ADS)

    Danzl, Johann G.; Sidenstein, Sven C.; Gregor, Carola; Urban, Nicolai T.; Ilgen, Peter; Jakobs, Stefan; Hell, Stefan W.

    2016-02-01

    Far-field super-resolution fluorescence microscopy discerns fluorophores residing closer than the diffraction barrier by briefly transferring them in different (typically ON and OFF) states before detection. In coordinate-targeted super-resolution variants, such as stimulated emission depletion (STED) microscopy, this state difference is created by the intensity minima and maxima of an optical pattern, causing all fluorophores to assume the off state, for instance, except at the minima. Although strong spatial confinement of the on state enables high resolution, it also subjects the fluorophores to excess intensities and state cycles at the maxima. Here, we address these issues by driving the fluorophores into a second off state that is inert to the excess light. By using reversibly switchable fluorescent proteins as labels, our approach reduces bleaching and enhances resolution and contrast in live-cell STED microscopy. Using two or more transitions to off states is a useful strategy for augmenting the power of coordinate-targeted super-resolution microscopy.

  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. 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...

  6. 34 CFR 76.580 - Coordination with other activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 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...

  7. 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

  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. 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

  10. Catalytically active lead(ii)-imidazolium coordination assemblies with diversified lead(ii) coordination geometries.

    PubMed

    Naga Babu, Chatla; Suresh, Paladugu; Srinivas, Katam; Sathyanarayana, Arruri; Sampath, Natarajan; Prabusankar, Ganesan

    2016-05-10

    Five Pb(ii)-imidazolium carboxylate coordination assemblies with novel structural motifs were derived from the reaction between the corresponding flexible, semi flexible or rigid imidazolium carboxylic acid ligands and lead nitrate. The imidazolium linker present in these molecules likely plays a triple role such as the counter ion to balance the metal charge, the ligand being an integral part of the final product and the catalyst facilitating carbon-carbon bond formation reaction. These lead-imidazolium coordination assemblies exhibit, variable chemical and thermal stabilities, as well as catalytic activity. These newly prepared catalysts are highly active towards benzoin condensation reactions with good functional group tolerance. PMID:27093629

  11. 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…

  12. 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

  13. 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.

  14. Multiple vehicle coordination and cooperative estimation for target tracking with applications to autonomous underwater vehicle systems

    NASA Astrophysics Data System (ADS)

    Triplett, Benjamin

    2008-07-01

    The subjects of Multi-vehicle coordinated control and fin-actuated underwater vehicles are receiving significant attention. Coordinated control is becoming more practical as advances in technology increase the areas of application in which systems of multiple vehicles could accomplish challenging tasks that are difficult or infeasible for a single vehicle to complete. Advances in sensor technology, improvements in wireless communication systems, and increases in microprocessor computation speed, all contribute to the creation of successful coordinated control systems. Coordinated target tracking, in which several pursuit autonomous pursuit vehicles follow and maintain state knowledge of a target vehicle, is the coordinated multiple-vehicle problem that is studied in this dissertation. Results show that multiple vehicles can be used to advantage in the target tracking problem, and that the sharing of target state information, whether data from measurements or estimates, improves the target tracking results. A fin-actuated underwater vehicle (FUV) was created as a hardware test platform for the application and study of both geometric methods in control and multiple-vehicle coordination. Combined with simulation based on geometric control methods, the FUV demonstrates remarkably good agreement between theory and experiment. Simple maneuvers such as forward swimming and turning, as well as more complicated agile maneuvers such as snap-turns are demonstrated by the robot and in simulation. Further, the robot is used with feedback control and radio communication in order to accomplish a number of individual and multi-vehicle tasks, such as radio-control, autonomous trajectory tracking, and coordinated heading control.

  15. 30 CFR 1229.122 - Coordination of audit activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... audit. This workplan must be submitted 120 days prior to the beginning of each fiscal year. A State may... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Coordination of audit activities. 1229.122... of audit activities. (a) Each State with a delegation of authority shall submit annually to the...

  16. 30 CFR 1229.122 - Coordination of audit activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... audit. This workplan must be submitted 120 days prior to the beginning of each fiscal year. A State may... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Coordination of audit activities. 1229.122... of audit activities. (a) Each State with a delegation of authority shall submit annually to the...

  17. 30 CFR 1229.122 - Coordination of audit activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... audit. This workplan must be submitted 120 days prior to the beginning of each fiscal year. A State may... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Coordination of audit activities. 1229.122... of audit activities. (a) Each State with a delegation of authority shall submit annually to the...

  18. 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)…

  19. Feature integration in visual working memory: parietal gamma activity is related to cognitive coordination.

    PubMed

    Morgan, Helen M; Muthukumaraswamy, Suresh D; Hibbs, Carina S; Shapiro, Kimron L; Bracewell, R Martyn; Singh, Krish D; Linden, David E J

    2011-12-01

    The mechanism by which distinct subprocesses in the brain are coordinated is a central conundrum of systems neuroscience. The parietal lobe is thought to play a key role in visual feature integration, and oscillatory activity in the gamma frequency range has been associated with perception of coherent objects and other tasks requiring neural coordination. Here, we examined the neural correlates of integrating mental representations in working memory and hypothesized that parietal gamma activity would be related to the success of cognitive coordination. Working memory is a classic example of a cognitive operation that requires the coordinated processing of different types of information and the contribution of multiple cognitive domains. Using magnetoencephalography (MEG), we report parietal activity in the high gamma (80-100 Hz) range during manipulation of visual and spatial information (colors and angles) in working memory. This parietal gamma activity was significantly higher during manipulation of visual-spatial conjunctions compared with single features. Furthermore, gamma activity correlated with successful performance during the conjunction task but not during the component tasks. Cortical gamma activity in parietal cortex may therefore play a role in cognitive coordination. PMID:21940605

  20. 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.

  1. 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.

  2. 42 CFR 476.104 - Coordination of activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Coordination of activities. 476.104 Section 476.104 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS QUALITY IMPROVEMENT ORGANIZATION REVIEW Review Responsibilities of Quality Improvement Organizations...

  3. 42 CFR 476.104 - Coordination of activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Coordination of activities. 476.104 Section 476.104 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control...

  4. 42 CFR 476.104 - Coordination of activities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Coordination of activities. 476.104 Section 476.104 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control...

  5. Setting Standards at the Forefront of Delivery System Reform: Aligning Care Coordination Quality Measures for Multiple Chronic Conditions

    PubMed Central

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

    2015-01-01

    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 health care providers and policymakers 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. PMID:24004040

  6. 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. PMID:24004040

  7. Hepatocyte nuclear factor 1 coordinates multiple processes in a model of intestinal epithelial cell function.

    PubMed

    Yang, Rui; Kerschner, Jenny L; Harris, Ann

    2016-04-01

    Mutations in hepatocyte nuclear factor 1 transcription factors (HNF1α/β) are associated with diabetes. These factors are well studied in the liver, pancreas and kidney, where they direct tissue-specific gene regulation. However, they also have an important role in the biology of many other tissues, including the intestine. We investigated the transcriptional network governed by HNF1 in an intestinal epithelial cell line (Caco2). We used chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) to identify HNF1 binding sites genome-wide. Direct targets of HNF1 were validated using conventional ChIP assays and confirmed by siRNA-mediated depletion of HNF1, followed by RT-qPCR. Gene ontology process enrichment analysis of the HNF1 targets identified multiple processes with a role in intestinal epithelial cell function, including properties of the cell membrane, cellular response to hormones, and regulation of biosynthetic processes. Approximately 50% of HNF1 binding sites were also occupied by other members of the intestinal transcriptional network, including hepatocyte nuclear factor 4A (HNF4A), caudal type homeobox 2 (CDX2), and forkhead box A2 (FOXA2). Depletion of HNF1 in Caco2 cells increases FOXA2 abundance and decreases levels of CDX2, illustrating the coordinated activities of the network. These data suggest that HNF1 plays an important role in regulating intestinal epithelial cell function, both directly and through interactions with other intestinal transcription factors. PMID:26855178

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

    PubMed Central

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

    2015-01-01

    Summary 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. PMID:25704949

  9. 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.

  10. Hand-eye coordination with an active camera head

    NASA Astrophysics Data System (ADS)

    Bishay, Magued; Peters, R. Alan; Wilkes, Don M.; Kawamura, Kazuhiko

    1997-09-01

    Hand-eye coordination is the coupling between vision and manipulation. Visual servoing is the term applied to hand-eye coordination in robots. In recent years, research has demonstrated that active vision -- active control of camera position and camera parameters -- facilitates a robot's interaction with the world. One aspect of active vision is centering an object in an image. This is known as gaze stabilization or fixation. This paper presents a new algorithm that applies target fixation to image-based visual servoing. This algorithm, called fixation point servoing (FPS), uses target fixation to eliminate the need for Jacobian computation Additionally, FPS reburies only the rotation relationship between the camera head and the gripper frames and does not require accurate tracking of the gripper. FPS was tested on a robotics system called ISAC and experimental results are shown. FPS was also compared to a classical Jacobian-based technique using simulations of both algorithms.

  11. 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

  12. 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

  13. 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…

  14. 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. PMID:25461433

  15. Multiple Identities and Education for Active Citizenship

    ERIC Educational Resources Information Center

    Ross, Alistair

    2007-01-01

    This paper explores concepts of multiple and nested identities and how these relate to citizenship and rights, and the implications of identities and rights for active citizenship education. Various theoretical conceptions of identity are analysed, and in particular ideas concerning multiple identities that are used contingently, and about…

  16. Activities of coordinated dietetic program directors compared by educational background.

    PubMed

    Nyland, N K; Spears, M C; Myers, E F

    1989-12-01

    This study was designed to ascertain the activities performed by coordinated program directors, compare current activities with 5-year expectations, and identify differences in importance and time spent on 14 pertinent activities by directors with master's degrees and those with doctorates. Responses were collected by a descriptive survey of 64 directors, all of whom participated. Program directors with master's degrees considered public relations with affiliations, attending faculty meetings, student advisement, and reading professional materials significantly more important (p less than .05) than did directors with doctorates, who considered faculty evaluations and research significantly more important (p less than .01). Directors with doctorates spent significantly less time in teaching (p less than .05) than those with master's degrees. Responsibilities of directors in the 22 submitted descriptions were organized into five categories: program management, curricular affairs, policies impacting on programs, student advisement and counseling, and academic activities. In the ADA Standards of Education, responsibilities of directors include program assessment, planning, and evaluation; in this study, those responsibilities were placed in the program management category. Exhibition of leadership qualities, revision of curriculum, and counseling and recruitment of students were responsibilities most frequently included in the position descriptions; however, those responsibilities were in categories other than program management. The responsibilities could serve as a guide for the development of a position description and as criteria for the role of a coordinated program director. PMID:2592717

  17. 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.

  18. 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.

  19. 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.

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

    PubMed

    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. ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms. PMID:26628093

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

    DOE PAGESBeta

    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

  2. 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

  3. 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

  4. 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

  5. Optimized measurement strategy for multiple-orientation technique on coordinate-measuring machines

    NASA Astrophysics Data System (ADS)

    Kondo, Yohan; Sasajima, Kazuyuki; Osawa, Sonko; Sato, Osamu; Watanabe, Tsukasa; Komori, Masaharu

    2009-10-01

    Coordinate-measuring machines (CMMs) are widely used to measure the characteristics of various geometrical features. The measurement results using CMMs include systematic errors. To eliminate the systematic errors, the multiple-orientation technique is effective for rotationally symmetric workpieces such as cylinders or gears. However, there are Fourier components of the calibration curve that cannot be analyzed on the basis of the number of orientations; therefore, the number of orientations was set to be larger than the number of required Fourier components. Such a method takes, however, a very long time and it is difficult to maintain a stable environment during the measurement. In this paper, we propose a new measurement strategy for reducing the total number of orientations by compensating the deficient Fourier components using the measurement result with another number of orientations. When the lowest common multiple of integers m and n is set to be larger than the number of required Fourier components, the calibration result can be obtained from m + n - 1 orientations. To select m and n most efficiently, the combination should not include a common prime number. The effectiveness of the combination measurement strategy for the multiple-orientation technique was demonstrated by calibrating a multiball artifact and a gear.

  6. 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

  7. Snail Coordinately Regulates Downstream Pathways to Control Multiple Aspects of Mammalian Neural Precursor Development

    PubMed Central

    Zander, Mark A.; Burns, Sarah E.; Yang, Guang; Kaplan, David R.

    2014-01-01

    The Snail transcription factor plays a key role in regulating diverse developmental processes but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal, and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway because coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts via p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology. PMID:24719096

  8. Molecular mechanisms of multiple toxin–antitoxin systems are coordinated to govern the persister phenotype

    PubMed Central

    Fasani, Rick A.; Savageau, Michael A.

    2013-01-01

    Toxin–antitoxin systems are ubiquitous and have been implicated in persistence, the multidrug tolerance of bacteria, biofilms, and, by extension, most chronic infections. However, their purpose, apparent redundancy, and coordination remain topics of debate. Our model relates molecular mechanisms to population dynamics for a large class of toxin–antitoxin systems and suggests answers to several of the open questions. The generic architecture of toxin–antitoxin systems provides the potential for bistability, and even when the systems do not exhibit bistability alone, they can be coupled to create a strongly bistable, hysteretic switch between normal and toxic states. Stochastic fluctuations can spontaneously switch the system to the toxic state, creating a heterogeneous population of growing and nongrowing cells, or persisters, that exist under normal conditions, rather than as an induced response. Multiple toxin–antitoxin systems can be cooperatively marshaled for greater effect, with the dilution determined by growth rate serving as the coordinating signal. The model predicts and elucidates experimental results that show a characteristic correlation between persister frequency and the number of toxin–antitoxin systems. PMID:23781105

  9. 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.

  10. 48 CFR 2452.237-72 - Coordination of data collection activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 (APR... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Coordination of...

  11. Subject specific coordination of two- and one-joint muscles during landings suggests multiple control criteria.

    PubMed

    McNitt-Gray, J L

    2000-01-01

    The target article, thoughtfully constructed by Dr. Prilutsky, effectively synthesizes available data on multijoint movements regarding coordination patterns of major two- and one-joint muscles, provides evidence for an optimization criterion that predicts critical features of muscle activation patterns, and explores the functional consequences of muscle coordination. This work also provides a clear set of definitions and an organizational framework that is currently needed for a productive interdisciplinary discussion regarding the underlying control mechanisms used during realistic multijoint movements. Although identification of an optimization criterion that predicts muscle recruitment strategies would greatly simplify control logic required for rehabilitation and musculoskeletal modeling, our experimental data during landings indicate more than one criterion may exist. Preliminary review of our experimental landing data suggests the rules identified by Prilutsky apparently hold for some subjects during portions of the landing movements. The presence of more than one muscle activation pattern used to achieve the same NJMs demonstrates there may be more than one optimization criterion that predicts critical features of muscle activation patterns. The functional consequences of more than one control criterion may also prove to be an asset, particularly when adapting to different environmental constraints. PMID:10675815

  12. 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)...

  13. 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...

  14. Selection of head and whisker coordination strategies during goal-oriented active touch.

    PubMed

    Schroeder, Joseph B; Ritt, Jason T

    2016-04-01

    In the rodent whisker system, a key model for neural processing and behavioral choices during active sensing, whisker motion is increasingly recognized as only part of a broader motor repertoire employed by rodents during active touch. In particular, recent studies suggest whisker and head motions are tightly coordinated. However, conditions governing the selection and temporal organization of such coordinated sensing strategies remain poorly understood. We videographically reconstructed head and whisker motions of freely moving mice searching for a randomly located rewarded aperture, focusing on trials in which animals appeared to rapidly "correct" their trajectory under tactile guidance. Mice orienting after unilateral contact repositioned their whiskers similarly to previously reported head-turning asymmetry. However, whisker repositioning preceded head turn onsets and was not bilaterally symmetric. Moreover, mice selectively employed a strategy we term contact maintenance, with whisking modulated to counteract head motion and facilitate repeated contacts on subsequent whisks. Significantly, contact maintenance was not observed following initial contact with an aperture boundary, when the mouse needed to make a large corrective head motion to the front of the aperture, but only following contact by the same whisker field with the opposite aperture boundary, when the mouse needed to precisely align its head with the reward spout. Together these results suggest that mice can select from a diverse range of sensing strategies incorporating both knowledge of the task and whisk-by-whisk sensory information and, moreover, suggest the existence of high level control (not solely reflexive) of sensing motions coordinated between multiple body parts. PMID:26792880

  15. 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

  16. 25 CFR 170.105 - Are funds available for consultation, collaboration, and coordination activities?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Are funds available for consultation, collaboration, and... Consultation, Collaboration, Coordination § 170.105 Are funds available for consultation, collaboration, and coordination activities? To fund consultation, collaboration, and coordination of IRR Program...

  17. 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

  18. 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.

  19. Using a co-ordinate measuring machine to align multiple element large optical systems

    NASA Astrophysics Data System (ADS)

    Howick, Eleanor F.; Cochrane, David; Meier, David

    2007-09-01

    A high precision Co-ordinate Measuring Machine (CMM) is an ideal instrument for aligning mid to large (400 to 600 mm) diameter multiple element lens assemblies. The CMM has many advantages over simpler dial gauge and rotary table setups. For example, these traditional methods do not necessarily make it easy to separate the out-of-roundness of a lens or its mounting cell, from a misalignment of the lens and cell. With a CMM, the 'as made' geometry of both the lenses and their mounting cells can be determined before the mounting and alignment process begins. By considering the actual shape of the lenses and cells, adjustments can be made during the alignment process to ensure that the complete assembly meets the designer's tolerances. This paper discusses CMM alignment techniques used and experience gained while assembling large lens corrector assemblies (for example, the three element Prime Focus Unit for FMOS, the Subaru Fibre Multi-Object Spectrograph) destined for installation in astronomical telescopes.

  20. Primary motor and sensory cortical areas communicate via spatiotemporally coordinated networks at multiple frequencies.

    PubMed

    Arce-McShane, Fritzie I; Ross, Callum F; Takahashi, Kazutaka; Sessle, Barry J; Hatsopoulos, Nicholas G

    2016-05-01

    Skilled movements rely on sensory information to shape optimal motor responses, for which the sensory and motor cortical areas are critical. How these areas interact to mediate sensorimotor integration is largely unknown. Here, we measure intercortical coherence between the orofacial motor (MIo) and somatosensory (SIo) areas of cortex as monkeys learn to generate tongue-protrusive force. We report that coherence between MIo and SIo is reciprocal and that neuroplastic changes in coherence gradually emerge over a few days. These functional networks of coherent spiking and local field potentials exhibit frequency-specific spatiotemporal properties. During force generation, theta coherence (2-6 Hz) is prominent and exhibited by numerous paired signals; before or after force generation, coherence is evident in alpha (6-13 Hz), beta (15-30 Hz), and gamma (30-50 Hz) bands, but the functional networks are smaller and weaker. Unlike coherence in the higher frequency bands, the distribution of the phase at peak theta coherence is bimodal with peaks near 0° and ±180°, suggesting that communication between somatosensory and motor areas is coordinated temporally by the phase of theta coherence. Time-sensitive sensorimotor integration and plasticity may rely on coherence of local and large-scale functional networks for cortical processes to operate at multiple temporal and spatial scales. PMID:27091982

  1. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling

    PubMed Central

    Shrestha, Yashaswi; Schafer, Eric J.; Boehm, Jesse S.; Thomas, Sapana R.; He, Frank; Du, Jinyan; Wang, Shumei; Barretina, Jordi; Weir, Barbara A.; Zhao, Jean J.; Polyak, Kornelia; Golub, Todd R.; Beroukhim, Rameen; Hahn, William C.

    2011-01-01

    Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK Mitogen-Activated Protein Kinase (MAPK) pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified PAK1 as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of Merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation. PMID:22105362

  2. 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.

  3. 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.

  4. 15 CFR 930.46 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COASTAL RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for... management program, but which have not yet begun, Federal agencies shall further coordinate with the State... coastal use or resource substantially different than originally described. Substantially different...

  5. 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.

  6. 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

  7. 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.

  8. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Coordination of AMRAP 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...

  9. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Coordination of AMRAP 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...

  10. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Coordination of AMRAP 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...

  11. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Coordination of AMRAP 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...

  12. 36 CFR 9.83 - Coordination of AMRAP activities in National Park System units.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Coordination of AMRAP 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...

  13. 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. PMID:25705194

  14. 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

  15. 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.

  16. Coordination and activation of azetidine by a triosmium cluster

    SciTech Connect

    Adams, R.D.; Chen, G. )

    1993-06-01

    The ring opening of nitrogen-containing heterocycles is an integral step in the process of hydrogenitrogenatio. The mechanisms by which this step occurs are poorly understood; thus a considerable amount of research has been devoted to modeling this heterogeneous reaction by using homogeneous catalysts. Although it has considerable ring strain, the four-membered heterocycle, azetidine, is opened thermally only at temperatures in excess of 400[degrees]C. Recently, we have found that thietanes, the saturated four-membered heterocycles containing sulfur, undergo facile ring opening when the molecule is coordinated to osmium cluster complexes. It was shown that a bridging coordination of the sulfur atom promotes this process. Thus, we wondered if it might also be possible to open an azetidine ring in a cluster complex under conditions sufficiently mild that a detailed study of the process might be possible. We have now prepared an osmium cluster complex in which the nitrogen atom of the azetidine ligand bridges two of the metal atoms, and we have found that the azetidine ring is spontaneously opened when the complex is heated to 125[degrees]C. In addition, two other complexes formed by transformation of the azetidine ligand have been isolated and characterized. The results of this study are reported here. 20 refs., 4 figs., 13 tabs.

  17. 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. PMID:24777209

  18. 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

  19. 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…

  20. 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…

  1. 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.…

  2. 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

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

    PubMed

    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

    2015-06-01

    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

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

    PubMed

    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

    2015-01-01

    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

  5. 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

  6. 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....

  7. 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

  8. Retinal waves coordinate patterned activity throughout the developing visual system

    PubMed Central

    Ackman, James B.; Burbridge, Timothy J.; Crair, Michael C.

    2014-01-01

    Summary The morphologic and functional development of the vertebrate nervous system is initially governed by genetic factors and subsequently refined by neuronal activity. However, fundamental features of the nervous system emerge before sensory experience is possible. Thus, activity-dependent development occurring before the onset of experience must be driven by spontaneous activity, but the origin and nature of activity in vivo remains largely untested. Here we use optical methods to demonstrate in live neonatal mice that waves of spontaneous retinal activity are present and propagate throughout the entire visual system before eye opening. This patterned activity encompassed the visual field, relied on cholinergic neurotransmission, preferentially initiated in the binocular retina, and exhibited spatiotemporal correlations between the two hemispheres. Retinal waves were the primary source of activity in the midbrain and primary visual cortex, but only modulated ongoing activity in secondary visual areas. Thus, spontaneous retinal activity is transmitted through the entire visual system and carries patterned information capable of guiding the activity-dependent development of complex intra- and inter- hemispheric circuits before the onset of vision. PMID:23060192

  9. 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

  10. A bio-inspired swarm robot coordination algorithm for multiple target searching

    NASA Astrophysics Data System (ADS)

    Meng, Yan; Gan, Jing; Desai, Sachi

    2008-04-01

    The coordination of a multi-robot system searching for multi targets is challenging under dynamic environment since the multi-robot system demands group coherence (agents need to have the incentive to work together faithfully) and group competence (agents need to know how to work together well). In our previous proposed bio-inspired coordination method, Local Interaction through Virtual Stigmergy (LIVS), one problem is the considerable randomness of the robot movement during coordination, which may lead to more power consumption and longer searching time. To address these issues, an adaptive LIVS (ALIVS) method is proposed in this paper, which not only considers the travel cost and target weight, but also predicting the target/robot ratio and potential robot redundancy with respect to the detected targets. Furthermore, a dynamic weight adjustment is also applied to improve the searching performance. This new method a truly distributed method where each robot makes its own decision based on its local sensing information and the information from its neighbors. Basically, each robot only communicates with its neighbors through a virtual stigmergy mechanism and makes its local movement decision based on a Particle Swarm Optimization (PSO) algorithm. The proposed ALIVS algorithm has been implemented on the embodied robot simulator, Player/Stage, in a searching target. The simulation results demonstrate the efficiency and robustness in a power-efficient manner with the real-world constraints.

  11. Coordinated sensing and active repair for self-healing

    NASA Astrophysics Data System (ADS)

    Hurley, D. A.; Huston, D. R.

    2011-02-01

    Self-repairing structural systems have the potential for improved performance ranges and lifetimes over conventional systems. Self-healing materials are not a new phenomenon and have been used in automotive and aeronautical applications for over a century. The bulk of these systems operate by using damage to directly initiate a repair response without any supervisory coordination. Integrating sensing and supervisory control technologies with self-healing may improve the safety and reliability of critical components and structures. This project illustrates the benefit of an integrated sensing, control, and self-healing system using laboratory scale test beds. A thermoplastic polymer embedded with resistive heating wires acts as the self-healing material. Damage is detected using an electro-optical sensing scheme based on photoresistors and a PC handling control duties. As damage occurs it is detected, located, and characterized. The key to this project is the integration of sensor feedback to control healing so that repairs are executed, monitored, and completed on the basis of continuous sensor data. This proof-of-concept prototype can likely be expanded and improved with alternative sensor options, self-healing materials, and system architecture.

  12. 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

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

    PubMed

    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, A-Lien; Toth, Eric A

    2013-12-01

    MutY homologue (MYH) is a DNA glycosylase which excises adenine paired with the oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxoG, or G(o)) 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

  14. 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

  15. Modified Active Site Coordination in a Clinical Mutant of Sulfite Oxidase

    SciTech Connect

    Doonan, C.J.; Wilson, H.L.; Rajagopalan, K.V.; Garrett, R.M.; Bennett, B.; Prince, R.C.; George, G.N.

    2009-06-02

    The molybdenum site of the Arginine 160 {yields} Glutamine clinical mutant of the physiologically vital enzyme sulfite oxidase has been investigated by a combination of X-ray absorption spectroscopy and density functional theory calculations. We conclude that the mutant enzyme has a six-coordinate pseudo-octahedral active site with coordination of Glutamine O{sup {epsilon}} to molybdenum. This contrasts with the wild-type enzyme which is five-coordinate with approximately square-based pyramidal geometry. This difference in the structure of the molybdenum site explains many of the properties of the mutant enzyme which have previously been reported.

  16. 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.

  17. 15 CFR 930.66 - Supplemental coordination for proposed activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COASTAL RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for... agency to be consistent with the management program, but which have not yet begun, applicants shall... proposed activity will affect any coastal use or resource substantially different than originally...

  18. 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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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.

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

    PubMed

    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

  2. Active Debris Removal of Multiple Priority Targets

    NASA Astrophysics Data System (ADS)

    Braun, Vitali; Flegel, Sven Kevin; Vörsmann, Peter; Wiedemann, Carsten; Gelhaus, Johannes; Moeckel, Marek; Kebschull, Christopher

    2012-07-01

    Today's space debris environment shows major concentrations of objects within distinct orbital regions for nearly all size regimes. The most critical region is found at orbital altitudes near 800 kilometers with high declinations. Within this region many satellites are operated in so called sun-synchronous orbits (SSO). Among those, there are Earth observation, communication and weather satellites. Due to the orbital geometry, head-on encounters with relative velocities of about 15 km/s are most probable and would thus result in highly energetic collisions, which are often referred to as catastrophic collisions, leading to the complete fragmentation of the participating objects. So called feedback collisions can then be triggered by the newly generated fragments, thus leading to a further population increase in the affected orbital region. This effect is known as the Kessler syndrome. Current studies show that catastrophic collisions are not a major problem today, but will become the main process for debris generation within the SSO region in the near future, even without any future launches. In order to avoid this effect, objects with a major impact on collisional cascading have to be actively removed from the critical region after their end of life. Not having the capability to perform an end-of-life maneuver in order to transfer to a graveyard orbit or to de-orbit, many satellites and rocket bodies would have to be de-orbited within a dedicated mission. In such a mission, a service satellite would perform a de-orbit maneuver, after having docked to a specific target. In this paper several systems, e.g. chemical and electrical engines are analysed with the main focus on removing multiple targets within one single mission. The service satellite has to undock from the previously de-orbited target in order to start the rendezvous and docking phase for a subsequent target. The targets are chosen from a previously defined priority list in order to enhance the mission

  3. Active debris removal of multiple priority targets

    NASA Astrophysics Data System (ADS)

    Braun, Vitali; Lüpken, A.; Flegel, S.; Gelhaus, J.; Möckel, M.; Kebschull, C.; Wiedemann, C.; Vörsmann, P.

    2013-05-01

    Today's space debris environment shows major concentrations of objects within distinct orbital regions for nearly all size regimes. The most critical region is found at orbital altitudes near 800 km with high declinations. Within this region many satellites are operated in so called sun-synchronous orbits (SSO). Among those, there are Earth observation, communication and weather satellites. Due to the orbital geometry in SSO, head-on encounters with relative velocities of about 15 km/s are most probable and would thus result in highly energetic collisions, which are often referred to as catastrophic collisions, leading to the complete fragmentation of the participating objects. So called feedback collisions can then be triggered by the newly generated fragments, thus leading to a further population increase in the affected orbital region. This effect is known as the Kessler syndrome.Current studies show that catastrophic collisions are not a major problem today, but will become the main process for debris generation within the SSO region in the near future, even without any further launches. In order to avoid this effect, objects with a major impact on collisional cascading have to be actively removed from the critical region after their end of life. Not having the capability to perform an end-of-life maneuver in order to transfer to a graveyard orbit or to de-orbit, many satellites and rocket bodies would have to be de-orbited within a dedicated mission. In such a mission, a service satellite would perform a de-orbit maneuver, after having docked to a specific target.In this paper, chemical and electric propulsion systems were analysed with the main focus on removing multiple targets within one single mission. The targets were chosen from a previously defined priority list in order to enhance the mission efficiency. Total mission time, ΔV and system mass were identified as key parameters to allow for an evaluation of the different concepts. It was shown that it

  4. Interdomain communications in bifunctional enzymes: how are different activities coordinated?

    PubMed

    Nagradova, Natalya

    2003-08-01

    Although bifunctional enzymes containing two different active centers located within separate domains are quite common in living systems, the significance of this bifunctionality is not always clear, and the molecular mechanisms of site-site interactions in such complex systems have come under the scrutiny of science only in recent years. This review summarizes recent data on the mechanisms of communication between active centers in bifunctional enzymes. Three types of enzymes are considered: (1) those catalyzing consecutive reactions of a metabolic pathway and exhibiting substrate channeling (glutamate synthase and imidazole glycerol phosphate synthase), (2) those catalyzing consecutive reactions without substrate channeling (lysine-ketoglutarate reductase/saccharopine dehydrogenase), and (3) those catalyzing opposed reactions (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). The functional role of interdomain communications is briefly discussed. PMID:14609201

  5. A Cautionary Tale About Conducting Research on Abstinence Education: How Do State Abstinence Coordinators Define "Sexual Activity?"

    ERIC Educational Resources Information Center

    Bailey, William; Young, Michael; Knickerbocker, Cliff; Doan, Tam

    2002-01-01

    Investigated how state coordinators of abstinence education programs defined "sexual activity." Researchers surveyed Title V abstinence education coordinators from the 50 states, the District of Columbia, and three territories. Of the 17 coordinators providing at least partial responses, none reported having a definition of sexual activity. The…

  6. 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

    ... COMMUNITY SERVICE EMPLOYMENT PROGRAM The State Senior Employment Services Coordination Plan § 641.335 How should the Governor address the coordination of SCSEP services with activities funded under title I of... coordination of SCSEP services with activities funded under title I of WIA? 641.335 Section 641.335...

  7. 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…

  8. Multiple-Object Tracking Is Based on Scene, Not Retinal, Coordinates

    ERIC Educational Resources Information Center

    Liu, Geniva; Austen, Erin L.; Booth, Kellogg S.; Fisher, Brian D.; Argue, Ritchie; Rempel, Mark I.; Enns, James T.

    2005-01-01

    This study tested whether multiple-object tracking-the ability to visually index objects on the basis of their spatiotemporal history-is scene based or image based. Initial experiments showed equivalent tracking accuracy for objects in 2-D and 3-D motion. Subsequent experiments manipulated the speeds of objects independent of the speed of the…

  9. Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

    PubMed Central

    Fang, Bin; Everett, Logan J.; Jager, Jennifer; Briggs, Erika; Armour, Sean M.; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A.

    2014-01-01

    SUMMARY Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. PMID:25416951

  10. 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…

  11. 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.

  12. Activities Coordinator. A Competency-Based Curriculum Designed To Prepare Students for Entry-Level Employment.

    ERIC Educational Resources Information Center

    Vocational Curriculum Resource Center of Maine, Fairfield.

    This curriculum was developed to assist instructors in planning and implementing a comprehensive, competency-based activities program to teach students skills for entry-level jobs as activities coordinators in nursing homes or extended-care facilities for older persons. The guide contains instructional units for each task listed on the job…

  13. 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.…

  14. 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…

  15. 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. PMID:24591120

  16. Active region studies with coordinated SOHO, microwave, and magnetograph observations

    NASA Technical Reports Server (NTRS)

    Holman, Gordon D.

    1992-01-01

    The scientific justification for an observing campaign to study the quantitative magnetic and plasma properties of coronal loops in active regions is presented. The SOHO (Solar and Heliospheric Observatory) instruments of primary relevance are CDS (Coronal Diagnostic Spectrometer), EIT, SUMER (Solar Ultraviolet Measurement of Emitted Radiation), and MDI. The primary ground based instruments would be the VLA (Very Large Array), the Owens Valley Radio Observatory, and vector and longitudinal field magnetographs. Similar campaigns have successfully been carried out with the Solar Maximum Mission x-ray polychromator and the Soft X-ray Imaging Sounding Rocket Payload (CoMStOC '87), the Goddard Solar EUV Rocket Telescope and Spectrograph, the Lockheed Solar Plasma Diagnostics Experiment rocket payload, and the Soft X-ray Telescope in Yohkoh (CoMStoc '92). The scientific payoff from such a campaign is discussed in light of the results from these previous campaigns.

  17. Coordination of maternal directives with preschoolers' behavior: influence of maternal coordination training on dyadic activity and child compliance.

    PubMed

    Strand, Paul S

    2002-03-01

    Investigated the impact of a specific intervention on child cooperation. The intervention was designed to increase maternal coordination with child behavior. Mothers assigned to the experimental condition were instructed on how to modulate the specificity of directives to their preschooler as a function of the child's moment-to-moment behavior. Mothers assigned to the control condition received no such training. Degree of maternal coordination was then assessed. Child compliance during a pick-up task was also assessed. Compared to controls, experimental mothers had significantly higher scores on several measures of maternal coordination and experimental children were significantly more compliant. The relation between parental coordination and child socialization is discussed. PMID:11845652

  18. 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

  19. Coordination of Fictive Motor Activity in the Larval Zebrafish Is Generated by Non-Segmental Mechanisms

    PubMed Central

    Wiggin, Timothy D.; Peck, Jack H.; Masino, Mark A.

    2014-01-01

    The cellular and network basis for most vertebrate locomotor central pattern generators (CPGs) is incompletely characterized, but organizational models based on known CPG architectures have been proposed. Segmental models propose that each spinal segment contains a circuit that controls local coordination and sends longer projections to coordinate activity between segments. Unsegmented/continuous models propose that patterned motor output is driven by gradients of neurons and synapses that do not have segmental boundaries. We tested these ideas in the larval zebrafish, an animal that swims in discrete episodes, each of which is composed of coordinated motor bursts that progress rostrocaudally and alternate from side to side. We perturbed the spinal cord using spinal transections or strychnine application and measured the effect on fictive motor output. Spinal transections eliminated episode structure, and reduced both rostrocaudal and side-to-side coordination. Preparations with fewer intact segments were more severely affected, and preparations consisting of midbody and caudal segments were more severely affected than those consisting of rostral segments. In reduced preparations with the same number of intact spinal segments, side-to-side coordination was more severely disrupted than rostrocaudal coordination. Reducing glycine receptor signaling with strychnine reversibly disrupted both rostrocaudal and side-to-side coordination in spinalized larvae without disrupting episodic structure. Both spinal transection and strychnine decreased the stability of the motor rhythm, but this effect was not causal in reducing coordination. These results are inconsistent with a segmented model of the spinal cord and are better explained by a continuous model in which motor neuron coordination is controlled by segment-spanning microcircuits. PMID:25275377

  20. 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.

  1. 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.

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

    PubMed Central

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

    2015-01-01

    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. PMID:26216900

  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. 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.

  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. '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. PMID:24635441

  7. Non-coordinating-Anion-Directed Reversal of Activation Site: Selective C-H Bond Activation of N-Aryl Rings.

    PubMed

    Wang, Dawei; Yu, Xiaoli; Xu, Xiang; Ge, Bingyang; Wang, Xiaoli; Zhang, Yaxuan

    2016-06-13

    An Rh-catalyzed selective C-H bond activation of diaryl-substituted anilides is described. In an attempt to achieve C-H activation of C-aryl rings, we unexpectedly obtained an N-aryl ring product under non-coordinating anion conditions, whereas the C-aryl ring product was obtained in the absence of a non-coordinating anion. This methodology has proved to be an excellent means of tuning and adjusting selective C-H bond activation of C-aryl and N-aryl rings. The approach has been rationalized by mechanistic studies and theoretical calculations. In addition, it has been found and verified that the catalytic activity of the rhodium catalyst is obviously improved by non-coordinating anions, which provides an efficient strategy for obtaining a highly chemoselective catalyst. Mechanistic experiments also unequivocally ruled out the possibility of a so-called "silver effect" in this transformation involving silver. PMID:27159169

  8. 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

  9. 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…

  10. 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

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

    PubMed

    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. 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

  13. Multiple plasma enzyme activities in liver disease

    PubMed Central

    Hargreaves, T.; Janota, I.; Smith, M. J. H.

    1961-01-01

    The measurement of the plasma activities of glutamic-oxaloacetic and glutamic-pyruvic transaminases, aldolase, cholinesterase, and isocitric, lactic, and phosphogluconic dehydrogenases in random samples of blood was found to be of no value in the differential diagnosis of hepatitis, obstructive jaundice, hepatic cirrhosis, and neoplastic conditions involving the liver. Serial determinations of the enzyme activities provided useful information about the course of certain hepatic disorders, particularly acute viral hepatitis. PMID:13711559

  14. 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…

  15. 25 CFR 170.105 - Are funds available for consultation, collaboration, and coordination activities?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Are funds available for consultation, collaboration, and coordination activities? 170.105 Section 170.105 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and...

  16. 25 CFR 170.105 - Are funds available for consultation, collaboration, and coordination activities?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Are funds available for consultation, collaboration, and coordination activities? 170.105 Section 170.105 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and...

  17. 25 CFR 170.105 - Are funds available for consultation, collaboration, and coordination activities?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Are funds available for consultation, collaboration, and coordination activities? 170.105 Section 170.105 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and...

  18. 25 CFR 170.105 - Are funds available for consultation, collaboration, and coordination activities?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Are funds available for consultation, collaboration, and coordination activities? 170.105 Section 170.105 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and...

  19. Coordinating and Performing Activities for Employer. Preparing Employer Itineraries, Student Manual and Teacher's Manual.

    ERIC Educational Resources Information Center

    Jones, Maleeta M.

    Supporting performance objective 12 of the V-TECS (Vocational-Technical Education Consortium of States) Secretarial Catalog, both a set of student materials and an instructor's manual on scheduling employer's trips are included in this packet. (The packet is the second in a set of four on coordinating and performing activities for the employer--CE…

  20. Coordinating and Performing Activities for Employer. Using Other Reference Materials. Student Manual and Teacher's Manual.

    ERIC Educational Resources Information Center

    Jones, Maleeta M.

    Supporting performance objective 45 of the V-TECS (Vocational-Technical Education Consortium of States) Secretarial Catalog, both a set of student materials and an instructor's manual on using reference books are included in this packet. (The packet is the third in a set of four on coordinating and performing activities for employers--CE 016…

  1. Bismuth coordination networks containing deferiprone: synthesis, characterisation, stability and antibacterial activity.

    PubMed

    Burrows, Andrew D; Jurcic, Monika; Mahon, Mary F; Pierrat, Sandrine; Roffe, Gavin W; Windle, Henry J; Spencer, John

    2015-08-21

    A series of bismuth-dicarboxylate-deferiprone coordination networks have been prepared and structurally characterised. The new compounds have been demonstrated to release the iron overload drug deferiprone on treatment with PBS and have also been shown to have antibacterial activity against H. pylori. PMID:26172618

  2. 48 CFR 2452.237-72 - Coordination of data collection activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Coordination of data collection activities. 2452.237-72 Section 2452.237-72 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts...

  3. 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.

  4. Multiple Arkadia/RNF111 structures coordinate its Polycomb body association and transcriptional control.

    PubMed

    Sun, Huaiyu; Liu, Yijing; Hunter, Tony

    2014-08-01

    The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming growth factor β (TGFβ) pathway. We previously identified Arkadia as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely how SUMO interaction contributes to the function of Arkadia was not resolved. Through analytical molecular and cell biology, we found that the SIMs share redundant function with Arkadia's M domain, a region distinguishing Arkadia from its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase (STUbL) RNF4. The SIMs and M domain together promote both Arkadia's colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation of a TGFβ pathway transcription reporter. Transcriptome profiling through RNA sequencing showed that Arkadia can both promote and inhibit gene expression, indicating that Arkadia's activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation. PMID:24912682

  5. Multiple Arkadia/RNF111 Structures Coordinate Its Polycomb Body Association and Transcriptional Control

    PubMed Central

    Liu, Yijing

    2014-01-01

    The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming growth factor β (TGFβ) pathway. We previously identified Arkadia as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely how SUMO interaction contributes to the function of Arkadia was not resolved. Through analytical molecular and cell biology, we found that the SIMs share redundant function with Arkadia's M domain, a region distinguishing Arkadia from its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase (STUbL) RNF4. The SIMs and M domain together promote both Arkadia's colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation of a TGFβ pathway transcription reporter. Transcriptome profiling through RNA sequencing showed that Arkadia can both promote and inhibit gene expression, indicating that Arkadia's activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation. PMID:24912682

  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. Active neutron multiplicity analysis and Monte Carlo calculations

    NASA Astrophysics Data System (ADS)

    Krick, M. S.; Ensslin, N.; Langner, D. G.; Miller, M. C.; Siebelist, R.; Stewart, J. E.; Ceo, R. N.; May, P. K.; Collins, L. L., Jr.

    Active neutron multiplicity measurements of high-enrichment uranium metal and oxide samples have been made at Los Alamos and Y-12. The data from the measurements of standards at Los Alamos were analyzed to obtain values for neutron multiplication and source-sample coupling. These results are compared to equivalent results obtained from Monte Carlo calculations. An approximate relationship between coupling and multiplication is derived and used to correct doubles rates for multiplication and coupling. The utility of singles counting for uranium samples is also examined.

  8. Active control technology and the use of multiple control surfaces

    NASA Technical Reports Server (NTRS)

    Hart, J. E.

    1976-01-01

    Needed criteria for active control technology applications in commercial transports are lacking. Criteria for redundancy requirements, believed to be consistent with certification philosophy, are postulated to afford a discussion of the relative value of multiple control surfaces. The control power and frequency bandpass requirements of various active control technology applications are shown to be such that multiple control surfaces offer advantages in minimizing the hydraulic or auxiliary power for the control surface actuators.

  9. 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

  10. Zn(II)-Coordinated Quantum Dot-FRET Nanosensors for the Detection of Protein Kinase Activity

    PubMed Central

    Lim, Butaek; Park, Ji-In; Lee, Kyung Jin; Lee, Jin-Won; Kim, Tae-Wuk; Kim, Young-Pil

    2015-01-01

    We report a simple detection of protein kinase activity using Zn(II)-mediated fluorescent resonance energy transfer (FRET) between quantum dots (QDs) and dye-tethered peptides. With neither complex chemical ligands nor surface modification of QDs, Zn(II) was the only metal ion that enabled the phosphorylated peptides to be strongly attached on the carboxyl groups of the QD surface via metal coordination, thus leading to a significant FRET efficiency. As a result, protein kinase activity in intermixed solution was efficiently detected by QD-FRET via Zn(II) coordination, especially when the peptide substrate was combined with affinity-based purification. We also found that mono- and di-phosphorylation in the peptide substrate could be discriminated by the Zn(II)-mediated QD-FRET. Our approach is expected to find applications for studying physiological function and signal transduction with respect to protein kinase activity. PMID:26213934

  11. 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. PMID:27164560

  12. Quality and coordination of care for patients with multiple conditions: results from an international survey of patient experience.

    PubMed

    Burgers, Jako S; Voerman, Gerlienke E; Grol, Richard; Faber, Marjan J; Schneider, Eric C

    2010-09-01

    Previous studies using clinical performance measures suggest that quality of care for patients with multiple chronic conditions is not worse than that for others. This article presents patient-reported experiences of health care among 8,973 of chronically ill adults from eight countries, using telephone survey data. We designed a ''morbidity score'' combining the number of conditions and reported health status. Respondents with high morbidity scores reported less favorable experience with coordination of care compared to those with low morbidity scores. They also reported lower ratings of overall quality of care. There were no differences in reported experience with the individual physicians. Comparing type of comorbidity, chronic lung, and mental health problems were associated with lower ratings than hypertension, heart disease, diabetes, arthritis, and cancer. The implications and limitations of this study are discussed in the context of health care reform. Pay-for-performance programs need to account for chronic conditions to avoid penalizing physicians who care for larger shares of such patients. PMID:20801976

  13. The Spring α-Helix Coordinates Multiple Modes of HCV (Hepatitis C Virus) NS3 Helicase Action.

    PubMed

    Gu, Meigang; Rice, Charles M

    2016-07-01

    Genomic DNA replication requires helicases to processively unwind duplexes. Although helicases encoded by positive-strand RNA viruses are necessary for RNA genome replication, their functions are not well understood. We determined structures of the hepatitis C virus helicase (NS3h) in complex with the transition state ATP mimic ADP·AlF4 (-) and compared them with the previous nucleic acid-associated ternary complexes. The results suggested that nucleic acid binding promotes a structural change of the spring helix at the transition state, optimizing the interaction network centered on the nucleophilic water. Analysis of ATP hydrolysis with and without conformational restraints on the spring helix further supported the importance of its action for both nucleic acid-stimulated and basal catalysis. We further found that an F238P substitution, predicted to destabilize the helix, diminished viral RNA replication without significantly affecting ATP-dependent duplex unwinding. The stability of the secondary structure, thus, seems critical for additional functions of NS3h. Taken together, the results suggest that the spring helix may be central to the coordination of multiple modes of NS3h action. Further characterization centered on this element may help understand the molecular details of how the viral helicase facilitates RNA replication. This new structural information may also aid efforts to develop specific inhibitors targeting this essential viral enzyme. PMID:27226535

  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. PMID:27586937

  15. Second Research Coordination Meeting on Reference Database for Neutron Activation Analysis -- Summary Report

    SciTech Connect

    Firestone, Richard B.; Kellett, Mark A.

    2008-03-19

    The second meeting of the Co-ordinated Research Project on"Reference Database for Neutron Activation Analysis" was held at the IAEA, Vienna from 7-9 May, 2007. A summary of the presentations made by participants is given, along with reports on specifically assigned tasks and subsequent discussions. In order to meet the overall objectives of this CRP, the outputs have been reiterated and new task assignments made.

  16. 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.

  17. 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

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

    PubMed

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

    2009-11-01

    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

  19. 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

  20. Body mass index, physical activity, and risk of multiple myeloma

    PubMed Central

    Birmann, Brenda M.; Giovannucci, Edward; Rosner, Bernard; Anderson, Kenneth C.; Colditz, Graham A.

    2013-01-01

    Several studies have reported a positive relation of baseline body mass index (BMI) with multiple myeloma, but data on other correlates of energy balance are limited. We undertook the present analyses to further examine the role of energy balance in multiple myeloma etiology in two large prospective cohorts with biennially updated exposure data. We followed members of the Nurses’ Health Study and Health Professionals Follow-up Study cohorts from baseline until multiple myeloma diagnosis, death, or 2002. Adult height and current weight were reported at enrollment, and weight every 2 years thereafter. Physical activity was queried at baseline and updated every 2-4 years. We computed age-adjusted relative risks (RR) of multiple myeloma for categories of BMI and physical activity using Cox proportional hazards regression. We conducted analyses on each cohort separately and on both cohorts combined. We confirmed 215 incident cases of multiple myeloma in the combined cohort of 136,623 individuals (>2.1 million person-years at risk). BMI was positively associated with multiple myeloma in all analyses. The association was strongest in men with BMI ≥30 kg/m2 (v. BMI <22.0 kg/m2; RR=2.4, 95% confidence interval (CI)=1.0-6.0) and modest in overweight (BMI 25-29.9 kg/m2) and obese (BMI ≥30 kg/m2) women (v. BMI <22.0 kg/m2; RR (95% CI)=1.6 (1.0-2.7) and 1.2 (0.7-2.2), respectively). Physical activity was not significantly related to multiple myeloma risk, although an inverse association was suggested in women. In conclusion, obesity appears to have an etiologic role in multiple myeloma, but the role of other correlates of energy balance remains uncertain. PMID:17627013

  1. Multiple active forms of thrombin. IV. Relative activities of meizothrombins

    SciTech Connect

    Doyle, M.F.; Mann, K.G. )

    1990-06-25

    The prothrombin activation intermediates meizothrombin and meizothrombin(desF1) (meizothrombin that has been autoproteolyzed to remove fragment 1) have been obtained in a relatively pure, active form with minimal autolysis, making them suitable for enzymatic characterization. When compared at equimolar concentrations, alpha-thrombin, fragment 1.2+ alpha-thrombin, meizothrombin(desF1), and meizothrombin have approximately 100, 100, 10, and 1% activity, respectively, toward the macromolecular substrates factor V, fibrinogen, and platelets. The difference in activity of these four enzymes cannot be attributed to alterations in the catalytic triad, as all four enzymes have nearly identical catalytic efficiency toward the chromogenic substrate S2238. Further, the ability of meizothrombin and meizothrombin(desF1) to activate protein C was 75% of the activity exhibited by alpha-thrombin or fragment 1.2+ alpha-thrombin. All four enzymes bind to thrombomodulin, as judged by the enhanced rate of protein C activation upon preincubation of the enzymes with thrombomodulin. The extent of rate enhancement varied, with meizothrombin/thrombomodulin exhibiting only 50% of the alpha-thrombin/thrombomodulin rate. This difference in rate is not due to a decreased affinity of the meizothrombin for thrombomodulin since the apparent dissociation constants for the alpha-thrombin-thrombomodulin complex and the meizothrombin-thrombomodulin complex are virtually identical. The difference in the observed rate is due in part to the higher Km for protein C exhibited by the meizothrombin-thrombomodulin complex. Incubation of the thrombomodulin-enzyme complex with phospholipid vesicles caused an increase in the protein C activation rates. The kinetic constants for protein C activation in the presence of phospholipid are virtually identical for these enzyme-thrombomodulin complexes.

  2. The Role of the Secondary Coordination Sphere in Metal-Mediated Dioxygen Activation

    PubMed Central

    Shook, Ryan L.

    2012-01-01

    Alfred Werner proposed nearly 100 years ago that the secondary coordination sphere has a role in determining physical properties of transition metal complexes. We now know that the secondary coordination sphere impacts nearly all aspects of transition metal chemistry, including the reactivity and selectivity in metal-mediated processes. These features are highlighted in the binding and activation of dioxygen by transition metal complexes. There are clear connections between the control of the secondary coordination sphere and the ability of metal complexes to 1) reversibly bind dioxygen or 2) bind and activate dioxygen to form highly reactive M–oxo complexes. In this forum article, several biological and synthetic examples are presented and discussed in terms of structure-function relationships. Particular emphasis is given to systems with defined non-covalent interactions, such as intramolecular hydrogen bonds involving dioxygen-derived ligands. To further illustrate these effects, the homolytic cleavage of C–H bonds by M–oxo complexes with basic oxo ligands is described. PMID:20380466

  3. 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.

  4. 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

  5. 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.

  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. 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. PMID:23893008

  8. 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…

  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. Coordination of software-development activities among sites that are geographically separated

    SciTech Connect

    Truett, L.F.; Loftis, J.P.; Shipe, P.C.; Faby, E.Z.; Grubb, J.W.

    1993-06-29

    The Department of Defense is sponsoring development of a centralized, integrated database, which will be a repository international surface cargo movement data. Scheduled for implementation surface in early 1994, the system will include a relational database management system, processing modules, and complex communication components. Four geographically separated sites are involved with development. Design and development of a major computer system is never simple, but when design and development occur at multiple sites, the problems are compounded, especially when the timeframe for project completion is extremely tight. Issues such as identical developmental platforms and communications strategies must be addressed. A design plan must be strictly followed to ensure consistency and to coordinate integration of modules developed at different sites.

  11. 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

  12. 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

  13. 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

  14. Coordinated activation of distinct Ca(2+) sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity.

    PubMed

    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

  15. 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

  16. HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability.

    PubMed

    Zhu, Min; Zhao, Hongchang; Liao, Ji; Xu, Xingzhi

    2014-12-01

    CLASPIN is an essential mediator in the DNA replication checkpoint, responsible for ATR (ataxia telangiectasia and Rad3-related protein)-dependent activation of CHK1 (checkpoint kinase 1). Here we found a dynamic signaling pathway that regulates CLASPIN turn over. Under unperturbed conditions, the E3 ubiquitin ligase HERC2 regulates the stability of the deubiquitinating enzyme USP20 by promoting ubiquitination-mediated proteasomal degradation. Under replication stress, ATR-mediated phosphorylation of USP20 results in the disassociation of HERC2 from USP20. USP20 in turn deubiquitinates K48-linked-polyubiquitinated CLASPIN, stabilizing CLASPIN and ultimately promoting CHK1 phosphorylation and CHK1-directed checkpoint activation. Inhibition of USP20 expression promotes chromosome instability and xenograft tumor growth. Taken together, our findings demonstrated a novel function of HERC2/USP20 in coordinating CHK1 activation by modulating CLASPIN stability, which ultimately promotes genome stability and suppresses tumor growth. PMID:25326330

  17. Falls and Physical Activity in Persons with Multiple Sclerosis

    PubMed Central

    Sosnoff, J. J.; Sandroff, B. M.; Pula, J. H.; Morrison, S. M.; Motl, R. W.

    2012-01-01

    Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P < .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P > .05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis. PMID:22966459

  18. 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.

  19. Lipid activation of the signal recognition particle receptor provides spatial coordination of protein targeting

    PubMed Central

    Lam, Vinh Q.; Akopian, David; Rome, Michael; Henningsen, Doug

    2010-01-01

    The signal recognition particle (SRP) and SRP receptor comprise the major cellular machinery that mediates the cotranslational targeting of proteins to cellular membranes. It remains unclear how the delivery of cargos to the target membrane is spatially coordinated. We show here that phospholipid binding drives important conformational rearrangements that activate the bacterial SRP receptor FtsY and the SRP–FtsY complex. This leads to accelerated SRP–FtsY complex assembly, and allows the SRP–FtsY complex to more efficiently unload cargo proteins. Likewise, formation of an active SRP–FtsY GTPase complex exposes FtsY’s lipid-binding helix and enables stable membrane association of the targeting complex. Thus, membrane binding, complex assembly with SRP, and cargo unloading are inextricably linked to each other via conformational changes in FtsY. These allosteric communications allow the membrane delivery of cargo proteins to be efficiently coupled to their subsequent unloading and translocation, thus providing spatial coordination during protein targeting. PMID:20733058

  20. Coordination of the Nuclear and Cytoplasmic Activities of p53 in Response to DNA Damage

    PubMed Central

    Pu, Tian; Zhang, Xiao-Peng; Liu, Feng; Wang, Wei

    2010-01-01

    The tumor suppressor p53 plays a key role in the cellular response to various stresses. Most previous studies have focused on either the nuclear or cytoplasmic proapoptotic functions of p53, ignoring the combination of both functions. To explore how the two functions of p53 are coordinated in the DNA damage response via computer simulation, we construct a model for the p53 network comprising coupled positive and negative feedback loops involving p53, Mdm2, and Akt, as well as PUMA and Bax. In our model p53 is stabilized and accumulates in the nucleus and cytoplasm upon DNA damage. Nuclear p53 induces expression of Mdm2, PTEN, PUMA, and Bax. Cytoplasmic p53 is then released from the p53·Bcl-xL complex by PUMA to activate Bax directly. We find that the switching between low and high protein levels underlies the decision between cell survival and death. Moreover, a balance between the nuclear and cytoplasmic p53 levels and appropriate levels of Akt and PUMA are required for reliable cell fate decision. Our results indicate that coordination of the transcription-dependent and -independent activities of p53 is important in determining cellular outcomes. These findings advance our understanding of the mechanism for p53-mediated cellular responses and provide clues to p53-based cancer therapy. PMID:20858413

  1. 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. PMID:25641070

  2. 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

  3. Multi-frequency activation of neuronal networks by coordinated reset stimulation

    PubMed Central

    Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

    2011-01-01

    We computationally study whether it is possible to stimulate a neuronal population in such a way that its mean firing rate increases without an increase of the population's net synchronization. For this, we use coordinated reset (CR) stimulation, which has previously been developed to desynchronize populations of oscillatory neurons. Intriguingly, delivered to a population of predominantly silent FitzHugh–Nagumo or Hindmarsh–Rose neurons at sufficient stimulation amplitudes, CR robustly causes a multi-frequency activation: different Arnold tongues such as 1 : 1 or n : m entrained neuronal clusters emerge, which consist of phase-shifted sub clusters. Owing to the clustering pattern the neurons' timing is well balanced, so that in total there is no synchronization. Our findings may contribute to the development of novel and safe stimulation treatments that specifically counteract cerebral hypo-activity without promoting pathological synchronization or inducing epileptic seizures. PMID:22419975

  4. 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.

  5. Hand-Arm Coordinated Manipulation Using Active Body-Environment Contact

    NASA Astrophysics Data System (ADS)

    Sugaiwa, Taisuke; Iwata, Hiroyasu; Sugano, Shigeki

    Human-symbiotic humanoid robots that can perform tasks dexterously with their hands are needed in our homes, welfare facilities, and other places. To improve their performance of tasks, we propose a scheme of controlling motion aimed at appropriately coordinated hand and arm motions. By observing human manual tasks, we identify an active body-environment contact as a kind of human manual skills and devise a motion control scheme based on it. We also analyze the effectiveness of the combination of the active body-environment contact and our proposed scheme in example tasks of the adding/removing constraint task. We validate our motion control scheme through actual tests on a prototype human-symbiotic humanoid robot.

  6. 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.

  7. 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.

  8. 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

  9. 45 CFR 287.140 - With whom should the Tribe coordinate in the operation of its work activities and services?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... operation of its work activities and services? 287.140 Section 287.140 Public Welfare Regulations Relating... and Operations § 287.140 With whom should the Tribe coordinate in the operation of its work activities and services? The administration of work activities and services provided under the NEW Program...

  10. 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. PMID:26276689

  11. Coordinated activation of premotor and ventromedial prefrontal cortices during vicarious reward

    PubMed Central

    Matsumoto, Madoka; Takahashi, Hidefumi; Yomogida, Yukihito; Matsumoto, Kenji

    2016-01-01

    The vicarious reward we receive from watching likable others obtaining a positive outcome is a pervasive phenomenon, yet its neural correlates are poorly understood. Here, we conducted a series of functional magnetic resonance imaging experiments to test the hypothesis that the brain areas responsible for action observation and reward processing work in a coordinated fashion during vicarious reward. In the first experiment (manipulation phase), the participant was instructed to cheer for a particular player in a two-player competitive game (Rock–Paper–Scissors). This manipulation made participants feel more unity with that player and resulted in unity-related activation in the premotor area during action observation. In the following main experiment, the participant witnessed the previously cheered-for or non-cheered-for player succeed in a new solitary game (a stopwatch game). The ventromedial prefrontal cortex (vmPFC) was activated when the cheered-for player succeeded in the game but not when the other player did. Interestingly, this vmPFC activation was functionally connected with premotor activation only during the cheered-for player’s success. These results suggest that vicarious reward is processed in the vmPFC-premotor network, which is activated specifically by the success of the other person with whom the individual feels unity and closeness. PMID:26500290

  12. 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

  13. 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

  14. 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

  15. Contributions to gene activation by multiple functions of Bicoid.

    PubMed Central

    Ma, X; Yuan, D; Scarborough, T; Ma, J

    1999-01-01

    Bicoid is a Drosophila morphogenetic protein required for the development of anterior structures in the embryo. To gain a better understanding of how Bicoid works as a transcriptional activator, we systematically analysed various functions of Bicoid required for gene activation. We provide evidence suggesting that Bicoid is an intrinsically weak activator. First, our biochemical experiments demonstrate that the Bicoid-DNA complexes are very unstable, suggesting a weak DNA-binding function of Bicoid. This idea is further supported by our experiments demonstrating that the same number of LexA-Bicoid fusion molecules can activate transcription more effectively from LexA sites than from Bicoid sites. Secondly, we demonstrate that transcriptional activation by the weak activator Bicoid is readily influenced by the local enhancer environment. These influences are decreased when the Bicoid function is enforced by attaching to it either a known dimerization domain or the strong activation domain VP16. VP16 can also compensate for the loss of some Bicoid sites in an enhancer element. Our experiments demonstrate that the outcome of transcriptional activation by Bicoid is determined by multiple weak functions that are interconnected, a finding that can further help us to understand how this morphogenetic protein achieves its molecular functions. PMID:10024522

  16. 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.

  17. 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.

  18. Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions

    PubMed Central

    Metz, Imke; Weigand, Stephen D; Popescu, Bogdan F G; Frischer, Josa M; Parisi, Joseph E; Guo, Yong; Lassmann, Hans; Brück, Wolfgang; Lucchinetti, Claudia F.

    2014-01-01

    Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Results Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. PMID:24771535

  19. New orally active proteasome inhibitors in multiple myeloma.

    PubMed

    Allegra, Alessandro; Alonci, Andrea; Gerace, Demetrio; Russo, Sabina; Innao, Vanessa; Calabrò, Laura; Musolino, Caterina

    2014-01-01

    Bortezomib is the first proteasome inhibitor approved for the therapy of multiple myeloma (MM). Although Bortezomib has renovated the treatment of MM, a considerable proportion of subjects fail to respond to Bortezomib treatment and almost all patients relapse from this drug either alone or when used in combination therapies. However, the good clinical outcome of Bortezomib treatment in MM patients gave impulsion for the development of second generation proteasome inhibitors with the ambition of improving efficacy of proteasome inhibition, enhancing antitumor activity, and decreasing toxicity, as well as providing flexible dosing schedules and patient convenience. This review provides an overview of the role of oral proteasome inhibitors including Marizomib, Oprozomib, Delanzomib, chemical proteasome inhibitors, and cinnabaramides, in the therapy of MM, focusing on developments over the past five years. These emerging drugs with different mechanisms of action have exhibited promising antitumor activity in patients with relapsed/refractory MM, and they are creating chances to target multiple pathways, overcome resistance, and improve clinical outcomes, mainly for those subjects who are refractory to approved agents. Future steps in the clinical development of oral inhibitors include the optimization of the schedule and the definition of their antitumor activity in MM. PMID:24239172

  20. 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

  1. Coordinate-based (ALE) meta-analysis of brain activation in patients with fibromyalgia.

    PubMed

    Dehghan, Mahboobeh; Schmidt-Wilcke, Tobias; Pfleiderer, Bettina; Eickhoff, Simon B; Petzke, Frank; Harris, Richard E; Montoya, Pedro; Burgmer, Markus

    2016-05-01

    There are an increasing number of neuroimaging studies that allow a better understanding of symptoms, neural correlates and associated conditions of fibromyalgia. However, the results of these studies are difficult to compare, as they include a heterogeneous group of patients, use different stimulation paradigms, tasks, and the statistical evaluation of neuroimaging data shows high variability. Therefore, this meta-analytic approach aimed at evaluating potential alterations in neuronal brain activity or structure related to pain processing in fibromyalgia syndrome (FMS) patients, using quantitative coordinate-based "activation likelihood estimation" (ALE) meta-analysis. 37 FMS papers met the inclusion criteria for an ALE analysis (1,264 subjects, 274 activation foci). A pooled ALE analysis of different modalities of neuroimaging and additional analyses according functional and structural changes indicated differences between FMS patients and controls in the insula, amygdala, anterior/mid cingulate cortex, superior temporal gyrus, the primary and secondary somatosensory cortex, and lingual gyrus. Our analysis showed consistent results across FMS studies with potential abnormalities especially in pain-related brain areas. Given that similar alterations have already been demonstrated in patients with other chronic pain conditions and the lack of adequate control groups of chronic pain subjects in most FMS studies, it is not clear however, whether these findings are associated with chronic pain in general or are unique features of patients with FMS. Hum Brain Mapp 37:1749-1758, 2016. © 2016 Wiley Periodicals, Inc. PMID:26864780

  2. 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

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

    PubMed Central

    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. PMID:26582917

  4. 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…

  5. Physical activity and pediatric multiple sclerosis: Developing a research agenda.

    PubMed

    Yeh, E Ann; Kinnett-Hopkins, Dominique; Grover, Stephanie A; Motl, Robert W

    2015-11-01

    Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life. PMID:26447061

  6. 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

  7. 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

  8. 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

  9. 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.

  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. 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.

  12. Active immunization therapies for Parkinson's disease and multiple system atrophy.

    PubMed

    Schneeberger, Achim; Tierney, Lanay; Mandler, Markus

    2016-02-01

    Vaccination is increasingly being investigated as a potential treatment for synucleinopathies, a group of neurodegenerative diseases including Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies associated with α-synuclein pathology. All lack a causal therapy. Development of novel, disease-altering treatment strategies is urgently needed. Vaccination has positioned itself as a prime strategy for addressing these diseases because it is broadly applicable, requires infrequent administration, and maintains low production costs for treating a large population or as a preventive measure. Current evidence points to a causal role of misfolded α-synuclein in the development and progression of synucleinopathies. In the past decade, significant progress in active immunization against α-synuclein has been shown both in preclinical animal models and in early clinical development. In this review, we describe the state-of-the-art in active immunization approaches to synucleinopathies, with a focus on advances in Parkinson's disease (PD) and multiple-system atrophy (MSA). We first review preclinical animal models, highlighting their progress in translation to the clinical setting. We then discuss current clinical applications, stressing different approaches taken to address α-synuclein pathology. Finally, we address challenges, trends, and future perspectives of current vaccination programs. PMID:26260853

  13. Activities-Specific Balance Confidence in People with Multiple Sclerosis

    PubMed Central

    Nilsagård, Ylva; Carling, Anna; Forsberg, Anette

    2012-01-01

    Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1–6). Outcome Measures. Timed Up and Go, Timed Up and Gocog, 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to −0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at α = 0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society. PMID:22919491

  14. 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.

  15. 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

  16. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia.

    PubMed

    McDonald, Braedon; Jenne, Craig N; Zhuo, Lisheng; Kimata, Koji; Kubes, Paul

    2013-12-01

    A key pathological feature of the systemic inflammatory response of sepsis/endotoxemia is the accumulation of neutrophils within the microvasculature of organs such as the liver, where they cause tissue damage and vascular dysfunction. There is emerging evidence that the vascular endothelium is critical to the orchestration of inflammatory responses to blood-borne microbes and microbial products in sepsis/endotoxemia. In this study, we aimed to understand the role of endothelium, and specifically endothelial TLR4 activation, in the regulation of neutrophil recruitment to the liver during endotoxemia. Intravital microscopy of bone marrow chimeric mice revealed that TLR4 expression by non-bone marrow-derived cells was required for neutrophil recruitment to the liver during endotoxemia. Furthermore, LPS-induced neutrophil adhesion in liver sinusoids was equivalent between wild-type mice and transgenic mice that express TLR4 only on endothelium (tlr4(-/-)Tie2(tlr4)), revealing that activation of endothelial TLR4 alone was sufficient to initiate neutrophil adhesion. Neutrophil arrest within sinusoids of endotoxemic mice requires adhesive interactions between neutrophil CD44 and endothelial hyaluronan. Intravital immunofluorescence imaging demonstrated that stimulation of endothelial TLR4 alone was sufficient to induce the deposition of serum-derived hyaluronan-associated protein (SHAP) within sinusoids, which was required for CD44/hyaluronan-dependent neutrophil adhesion. In addition to endothelial TLR4 activation, Kupffer cells contribute to neutrophil recruitment via a distinct CD44/HA/SHAP-independent mechanism. This study sheds new light on the control of innate immune activation within the liver vasculature during endotoxemia, revealing a key role for endothelial cells as sentinels in the detection of intravascular infections and coordination of neutrophil recruitment to the liver. PMID:24113769

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

    PubMed Central

    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. PMID:26699865

  18. Motor ability and weight status are determinants of out-of-school activity participation for children with developmental coordination disorder.

    PubMed

    Fong, Shirley S M; Lee, Velma Y L; Chan, Nerita N C; Chan, Rachel S H; Chak, Wai-Kwong; Pang, Marco Y C

    2011-01-01

    According to the International Classification of Functioning, Disability and Health model endorsed by the World Health Organization, participation in everyday activities is integral to normal child development. However, little is known about the influence of motor ability and weight status on physical activity participation in children with developmental coordination disorder (DCD). This study aimed to (1) compare motor performance, weight status and pattern of out-of-school activity participation between children with DCD and those without; and (2) identify whether motor ability and weight status were determinants of participation patterns among children with DCD. We enrolled 81 children with DCD (boys, n = 63; girls, n = 18; mean age, 8.07 ± 1.5 years) and 67 typically developing children (boys, n = 48; girls, n = 19; mean age, 8.25 ± 1.6 years). Participation patterns (diversity, intensity, companionship, location, and enjoyment) were evaluated with the Children Assessment of Participation and Enjoyment. Motor ability was evaluated with the Movement Assessment Battery for Children, second edition (MABC-2). Other factors that may influence participation such as age, gender, and body weight were also recorded. Analysis of variance was used to compare outcome variables of the two groups, and significant determinants of activity participation were identified by multiple regression analysis. Children with DCD participated in fewer activities (i.e., limited participation diversity) and participated less frequently (i.e., limited participation intensity) than their typically developing peers; however, companionship, location of participation, and enjoyment level did not differ between the two groups. Children in the DCD group demonstrated significantly worse motor ability as assessed by the MABC-2. Further, a greater proportion of children in the DCD group were in the overweight/obese category compared with their typically developing peers. After accounting for the

  19. 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. PMID:18206349

  20. Activation of multiple signaling modules is critical in angiotensin IV-induced lung endothelial cell proliferation.

    PubMed

    Li, Yong D; Block, Edward R; Patel, Jawaharlal M

    2002-10-01

    Signaling events involving angiotensin IV (ANG IV)-mediated pulmonary artery endothelial cell (PAEC) proliferation were examined. ANG IV significantly increased upstream phosphatidylinositide (PI) 3-kinase (PI3K), PI-dependent kinase-1 (PDK-1), extracellular signal-related kinases (ERK1/2), and protein kinase B-alpha/Akt (PKB-alpha) activities, as well as downstream p70 ribosomal S6 kinase (p70S6K) activities and/or phosphorylation of these proteins. ANG IV also significantly increased 5-bromo-2'-deoxy-uridine incorporation into newly synthesized DNA in a concentration- and time-dependent manner. Pretreatment of cells with wortmannin and LY-294002, inhibitors of PI3K, or rapamycin, an inhibitor of the mammalian target of rapamycin kinase and p70S6K, diminished the ANG IV-mediated activation of PDK-1 and PKB-alpha as well as phosphorylation of p70S6K. Although an inhibitor of mitogen-activated protein kinase kinase, PD-98059, but not rapamycin, blocked ANG IV-induced phosphorylation of ERK1/2, both PD-98059 and rapamycin independently caused partial reduction in ANG IV-mediated cell proliferation. However, simultaneous treatment with PD-98059 and rapamycin resulted in total inhibition of ANG IV-induced cell proliferation. These results demonstrate that ANG IV-induced DNA synthesis is regulated in a coordinated fashion involving multiple signaling modules in PAEC. PMID:12225947

  1. 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

  2. Active joint mechanism driven by multiple actuators made of flexible bags: a proposal of dual structural actuator.

    PubMed

    Kimura, Hitoshi; Matsuzaki, Takuya; Kataoka, Mokutaro; 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

  3. Myeloid cell distribution and activity in multiple sclerosis.

    PubMed

    Moliné-Velázquez, Verónica; Vila-Del Sol, Virginia; de Castro, Fernando; Clemente, Diego

    2016-04-01

    Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this neurological disease. The destruction of myelin due to the uncontrolled activity of the invading immune cells leads to the formation of MS plaques. Among the different leukocytes that participate in the immune response associated with MS, the role of myeloid cells has been analyzed extensively (i.e. macrophages, dendritic cells -DCs- and neutrophils). Hence, in this review we will summarize what is known about the distribution, expression and markers available to study myeloid cells, and their histopathology, not only in a standard animal model of MS (autoimmune experimental encephalomyelitis -EAE) but also in MS tissue. In this review, we will not only refer to mature myeloid cells but also to the undifferentiated and almost unexplored myeloid-derived suppressor cells (MDSCs). The active role of MDSCs in the prompt resolution of an immune episode is gaining importance, yet is still the subject of some debate. Finally, the similarities and differences between MS and EAE are discussed, particularly in terms of myeloid cell phenotype, activity and the markers used. PMID:26592711

  4. 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. PMID:25653584

  5. 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

  6. BRCA2 Coordinates the Activities of Cell-Cycle Kinases to Promote Genome Stability

    PubMed Central

    Yata, Keiko; Bleuyard, Jean-Yves; Nakato, Ryuichiro; Ralf, Christine; Katou, Yuki; Schwab, Rebekka A.; Niedzwiedz, Wojciech; Shirahige, Katsuhiko; Esashi, Fumiko

    2014-01-01

    Summary Numerous human genome instability syndromes, including cancer, are closely associated with events arising from malfunction of the essential recombinase Rad51. However, little is known about how Rad51 is dynamically regulated in human cells. Here, we show that the breast cancer susceptibility protein BRCA2, a key Rad51 binding partner, coordinates the activity of the central cell-cycle drivers CDKs and Plk1 to promote Rad51-mediated genome stability control. The soluble nuclear fraction of BRCA2 binds Plk1 directly in a cell-cycle- and CDK-dependent manner and acts as a molecular platform to facilitate Plk1-mediated Rad51 phosphorylation. This phosphorylation is important for enhancing the association of Rad51 with stressed replication forks, which in turn protects the genomic integrity of proliferating human cells. This study reveals an elaborate but highly organized molecular interplay between Rad51 regulators and has significant implications for understanding tumorigenesis and therapeutic resistance in patients with BRCA2 deficiency. PMID:24835992

  7. Activation of Elemental Sulfur at a Two-Coordinate Platinum(0) Center.

    PubMed

    Roy, Sudipta; Schürmann, Christian J; Mondal, Totan; Koley, Debasis; Herbst-Irmer, Regine; Stalke, Dietmar; Roesky, Herbert W

    2016-08-26

    Platinum dichalcogenides have been known to exhibit two-dimensional layered structures. Herein, we describe the syntheses, isolation, and characterization of air-stable crystalline cyclic alkyl(amino) carbene (cAAC)-supported monomeric platinum disulfide three-membered ring complex [(cAAC)2 Pt(S2 )] (2). The highly reactive platinum(0) [(cAAC)2 Pt] complex (1) with two-coordinate platinum activates elemental sulfur to give 2. The brown crystals of bis-carbene platinum(II)monosulfate [(cAAC)2 Pt(SO4 )x (S2 )1-x ] (4) have been isolated when the reaction was performed in air. The dioxygen analogue of 2 was formed upon exposing the THF solution of 1 to aerial oxygen (O2 ). The binding of oxygen at the Pt(0) center was found to be reversible. Additionally, DFT study has been performed to elucidate the electronic structure and bonding scenario of 2, 3, and 4. Quantum chemical calculations showed donor-acceptor-type interaction for the Pt-S bonds in 2 and Pt-O bonds in 3 and 4. PMID:27414489

  8. 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.

  9. 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

  10. 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...

  11. EXEL; Experience for Children in Learning. Parent-Directed Activities to Develop: Oral Expression, Visual Discrimination, Auditory Discrimination, Motor Coordination.

    ERIC Educational Resources Information Center

    Behrmann, Polly; Millman, Joan

    The activities collected in this handbook are planned for parents to use with their children in a learning experience. They can also be used in the classroom. Sections contain games designed to develop visual discrimination, auditory discrimination, motor coordination and oral expression. An objective is given for each game, and directions for…

  12. 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…

  13. Neuronal activity related to eye-hand coordination in the primate premotor cortex.

    PubMed

    Jouffrais, C; Boussaoud, D

    1999-09-01

    To test the functional implications of gaze signals that we previously reported in the dorsal premotor cortex (PMd), we trained two rhesus monkeys to point to visual targets presented on a touch screen while controlling their gaze orientation. Each monkey had to perform four different tasks. To initiate a trial, the monkey had to put his hand on a starting position at the center of the touch screen and fixate a fixation point. In one task, the animal had to make a reaching movement to a peripheral target randomly presented at one of eight possible locations on a circle while maintaining fixation at the center of this virtual circle (central fixation + reaching). In the second task, the monkey maintained fixation at the location of the upcoming peripheral target and, later, reached to that location. After a delay, the target was turned on and the monkey made a reaching arm movement (target fixation + reaching). In the third task, the monkey made a saccade to the target without any arm movement (saccade). Finally, in the fourth task, the monkey first made a saccade to the target, then reached to it after a delay (saccade + reaching). This design allowed us to examine the contribution of the oculomotor context to arm-related neuronal activity in PMd. We analyzed the effects of the task type on neuronal activity and found that many cells showed a task effect during the signal (26/60; 43%), set (16/49; 33%) and/or movement (15/54; 28%) epochs, depending on the oculomotor history. These findings, together with previously published data, suggest that PMd codes limb-movement direction in a gaze-dependent manner and may, thus, play an important role in the brain mechanisms of eye-hand coordination during visually guided reaching. PMID:10473760

  14. 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

  15. 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

  16. Mouse Visual Neocortex Supports Multiple Stereotyped Patterns of Microcircuit Activity

    PubMed Central

    Sadovsky, Alexander J.

    2014-01-01

    Spiking correlations between neocortical neurons provide insight into the underlying synaptic connectivity that defines cortical microcircuitry. Here, using two-photon calcium fluorescence imaging, we observed the simultaneous dynamics of hundreds of neurons in slices of mouse primary visual cortex (V1). Consistent with a balance of excitation and inhibition, V1 dynamics were characterized by a linear scaling between firing rate and circuit size. Using lagged firing correlations between neurons, we generated functional wiring diagrams to evaluate the topological features of V1 microcircuitry. We found that circuit connectivity exhibited both cyclic graph motifs, indicating recurrent wiring, and acyclic graph motifs, indicating feedforward wiring. After overlaying the functional wiring diagrams onto the imaged field of view, we found properties consistent with Rentian scaling: wiring diagrams were topologically efficient because they minimized wiring with a modular architecture. Within single imaged fields of view, V1 contained multiple discrete circuits that were overlapping and highly interdigitated but were still distinct from one another. The majority of neurons that were shared between circuits displayed peri-event spiking activity whose timing was specific to the active circuit, whereas spike times for a smaller percentage of neurons were invariant to circuit identity. These data provide evidence that V1 microcircuitry exhibits balanced dynamics, is efficiently arranged in anatomical space, and is capable of supporting a diversity of multineuron spike firing patterns from overlapping sets of neurons. PMID:24899701

  17. Dynamics of biomembranes with active multiple-state inclusions.

    PubMed

    Chen, Hsuan-Yi; Mikhailov, Alexander S

    2010-03-01

    Nonequilibrium dynamics of biomembranes with active multiple-state inclusions is considered. The inclusions represent protein molecules which perform cyclic internal conformational motions driven by the energy brought with adenosine triphosphate (ATP) ligands. As protein conformations cyclically change, this induces hydrodynamical flows and also directly affects the local curvature of a membrane. On the other hand, variations in the local curvature of the membrane modify the transition rates between conformational states in a protein, leading to a feedback in the considered system. Moreover, active inclusions can move diffusively through the membrane so that their surface concentration varies. The kinetic description of this system is constructed and the stability of the uniform stationary state is analytically investigated. We show that, as the rate of supply of chemical energy is increased above a certain threshold, this uniform state becomes unstable and stationary or traveling waves spontaneously develop in the system. Such waves are accompanied by periodic spatial variations of the membrane curvature and the inclusion density. For typical parameter values, their characteristic wavelengths are of the order of hundreds of nanometers. For traveling waves, the characteristic frequency is of the order of a thousand Hz or less. The predicted instabilities are possible only if at least three internal inclusion states are present. PMID:20365764

  18. 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

  19. Effect of axial coordination on the electronic structure and biological activity of dirhodium(II,II) complexes.

    PubMed

    Aguirre, J Dafhne; Lutterman, Daniel A; Angeles-Boza, Alfredo M; Dunbar, Kim R; Turro, Claudia

    2007-09-01

    The reactivities toward biomolecules of a series of three dirhodium(II,II) complexes that possess an increasing number of accessible axial coordination sites are compared. In cis-[Rh2(OAc)2(np)2]2+ (1; np=1,8-naphthyridine) both axial sites are available for coordination, whereas for cis-[Rh2(OAc)2(np)(pynp)]2+ (2; pynp=2-(2-pyridyl)1,8-naphthyridine) and cis-[Rh2(OAc)2(pynp)2]2+ (3) the bridging pynp ligand blocks one and two of the axial coordination sites in the complexes, respectively. The electronic absorption spectra of the complexes are consistent with strong metal-to-ligand charge transfer transitions at low energy and ligand-centered peaks localized on the np and/or pynp ligands in the UV and near-UV regions. Time-dependent density functional theory calculations were used to aid in the assignments. The three complexes exhibit metal-centered oxidations and reductions, localized on the aromatic ligands. The ability of the complexes to stabilize duplex DNA and to inhibit transcription in vitro is greatly affected by the availability of an open axial coordination site. The present work shows that open axial coordination sites on the dirhodium complexes are necessary for biological activity. PMID:17685607

  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. 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

  2. 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.

  3. 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.

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

    PubMed Central

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

    2015-01-01

    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

  5. 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

  6. 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.

  7. Multiple Active Volcanoes in the Northeast Lau Basin

    NASA Astrophysics Data System (ADS)

    Baker, E. T.; Resing, J. A.; Lupton, J. E.; Walker, S. L.; Embley, R. W.; Rubin, K. H.; Buck, N.; de Ronde, C. E.; Arculus, R. J.

    2010-12-01

    The northeast Lau Basin occupies a complex geological area between the Tafua arc front, the E-W trending Tonga Trench, and the Northeast Lau Spreading Center. These boundaries create multiple zones of extension and thus provide abundant opportunities for magma to invade the crust. The 25-km-long chain of “Mata” volcanoes lies near the center of this area, separated from both the arc front and the spreading ridge. In 2008 we discovered hydrothermal venting on the largest and most southerly of these volcanoes, W and E Mata. In 2010 we visited the 7 smaller volcanoes that form a 15-km-long arcuate sweep to the north from W and E Mata (the “North Matas”). We also revisited W and E Mata. Over each volcano we conducted CTD tows to map plumes and collect water samples. Based on the CTD results, camera tows searched for seafloor sources on three volcanoes. The N Mata volcanoes, extending from Mata Taha (1) in the south to Mata Fitu (7) in the north, lie within a prominent gap in the shallow bathymetry along the southern border of the Tonga trench. Northward from E Mata the Mata volcanoes degrade from large symmetrical cones to smaller and blocky volcanic edifices. Summit depths range from 1165 m (W Mata) to 2670 m (Mata Nima (5)). The most active volcano in the chain is the erupting W Mata, with an intense plume that extended 250 m above the summit. Hydrothermal temperature anomalies (Δθ, corrected for hydrographic masking effects) reached ˜1.7°C, with light-scattering values as high as 2-5 ΔNTU. The 2010 surveys now show that 6 of the 7 N Mata volcanoes are also hydrothermally active. Along the N Matas, Δθ and ΔNTU signals ranged from robust to weak, but distinct oxidation-reduction potential (aka Eh) anomalies confirmed active venting in each case. The most concentrated plumes were found near Mata Ua (2) and Mata Fitu (7), with Δθ and ΔNTU maxima of 0.1-0.17°C and 0.3, respectively. Despite the variability in plume strength, however, ΔNTU/Δθ ratios

  8. Active beam shaping in multiple laser guide stars

    NASA Astrophysics Data System (ADS)

    Jones, Katharine J.

    2012-10-01

    Adaptive beam shaping is a critical part of multiple Laser Guide Stars (LGS) for Multiple Conjugate Adaptive Optics (MCAO) for ground-based astronomical telescopes. There are two kinds of Laser Guide Stars: Na Laser Guide Stars (at 589 nm and 92 km altitude) and Rayleigh Laser Guide Stars (at 532 nm and 20 km altitude). Multiple Conjugate Adaptive Optics (MCAO) corrects for each "layer" of atmosphere independently. Multiple Laser Guide Stars are being developed to achieve a measure of tilt and increase the isoplanatic patch. Multiple Laser Guide Stars are being combined with Multiple Conjugate Optics in the Large Binocular Telescope (LBT): more than one Laser Guide Star (4-5) and two different wavelengths: 589 nm and 532 nm. Other observatories have multiple Laser Guide Stars but only one wavelength: 589 nm or 532 nm. Because Laser Guide Stars are launched into the atmosphere, adaptive beam shaping will be carried out before the laser is launched and will be different depending on which laser is being used, presumably to effect the tightest beam which can be achieved at the power level which is required to provide the requisite return to gound-based wavefront sensors. A complete range of devices are used. Beam attenuation and divergnece will take place. Multiple Laser Guide Stars of major observatories (SOR, LBT, MMT, ESO VLT and Gemini South) will be evaluated for effective adaptive beam shaping and impact on performance

  9. 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...

  10. Coordinating and Performing Activities for Employer. Preparing Expense Reports. Student Manual and Teacher's Manual.

    ERIC Educational Resources Information Center

    Jones, Maleeta M.

    Supporting performance objective 13 of the V-TECS (Vocational-Technical Education Consortium of States) Secretarial Catalog, both a set of student materials and an instructor's manual on preparing employer's business expense statements are included in this packet. (The packet is the fourth in a set of four on coordinating and performing activities…

  11. 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…

  12. 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.

  13. 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

    2016-05-01

    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.

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

    PubMed Central

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

    2007-01-01

    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 6 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, as 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 room-based representations). PMID:17959742

  15. 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.

  16. 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

  17. Optimized coordination of brakes and active steering for a 4WS passenger car.

    PubMed

    Tavasoli, Ali; Naraghi, Mahyar; Shakeri, Heman

    2012-09-01

    Optimum coordination of individual brakes and front/rear steering subsystems is presented. The integrated control strategy consists of three modules. A coordinated high-level control determines the body forces/moment required to achieve vehicle motion objectives. The body forces/moment are allocated to braking and steering subsystems through an intermediate unit, which integrates available subsystems based on phase plane notion in an optimal manner. To this end, an optimization problem including several equality and inequality constraints is defined and solved analytically, such that a real-time implementation can be realized without the use of numeric optimization software. A low-level slip-ratio controller works to generate the desired longitudinal forces at small longitudinal slip-ratios, while averting wheel locking at large slip-ratios. The efficiency of the suggested approach is demonstrated through computer simulations. PMID:22749293

  18. 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

  19. 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

  20. [The psychomotor test for research of eye-hand coordination at performance of monotonous activity on tracking target].

    PubMed

    Dorokhov, V B; Arsen'ev, G N; Tkachenko, O N; Zakharchenko, D V; Lavrova, T P; Dementienko, V V

    2011-01-01

    Visual-motor coordination is necessary for successful performance of everyday activities. Many tasks, such as driving or operating devices in the workplace, require a variety of coordination patterns with different levels of compatibility between the eyes and the hand. The psychomotor test was developed which makes it possible to analyze visual-motor coordination disorders caused by a decrease in the level of wakefulness. A small circular target (14 mm in diameter) was moving with a low constant velosity (12 mm/s) in a circular trajectory (80 mm in diameter) with a period of 20 s. Subjects were instructed to keep the mouse-driven cursor inside a target, overstepping the limits of the moving target was considered as an error. To test the attention level, an additional stimulus was introduced which appeared for 3 seconds with an interval of 15 to 40 s. When the stimulus appeared, it was required to touch it with the cursor and click the mouse button. Cursor trajectories have a temporal resolution of 120 Hz. Eye movements were recorded with a PC-based Eyegaze Development System (LC Technologies, USA) measuring corneal reflectance with a collection rate of 120 Hz. Monotonous character of the test performance induced drowsiness and led to errors 25-30 minutes after the beginning of the experiment. Changes in physiological vigilance level was evaluated with EEG recording. Analysis of the dynamic characteristics of smooth and saccadic eye movements and hand movements showed their high sensitivity to a decrease in efficiency of operator's activity caused by a drop in the level of wakefulness. It is suggested that further development of this approach to measuring eye-hand coordination will promote working out a contactless method for the express diagnostics of the critical levels of drowsiness as well as for the definition of professional characteristics of an operator. PMID:21961322

  1. 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.

  2. 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.

  3. Effects of Project Activities Based on Multiple Intelligences to Elementary School Children's Science Achievement.

    ERIC Educational Resources Information Center

    Lim, Chaeseong; Wang, Kyungsoon

    2001-01-01

    Examines the influence of project activities based on multiple intelligences on the science achievement of elementary school children. Explains the proportions of variance of science achievement by General Intelligence (GI), analyzes Multiple Intelligences (MI), and investigates the influence of project activities that used various aspects of MI.…

  4. Beyond the active site: the impact of the outer coordination sphere on electrocatalysts for hydrogen production and oxidation.

    PubMed

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

    2014-08-19

    Redox active metalloenzymes play a major role in energy transformation reactions in biological systems. Examples include formate dehydrogenases, nitrogenases, CO dehydrogenase, and hydrogenases. Many of these reactions are also of interest to humans as potential energy storage or utilization reactions for photoelectrochemical, electrolytic, and fuel cell applications. These metalloenzymes consist of redox active metal centers where substrates are activated and undergo transformation to products accompanied by electron and proton transfer to or from the substrate. These active sites are typically buried deep within a protein matrix of the enzyme with channels for proton transport, electron transport, and substrate/product transport between the active site and the surface of the protein. In addition, there are amino acid residues that lie in close proximity to the active site that are thought to play important roles in regulating and enhancing enzyme activity. Directly studying the outer coordination sphere of enzymes can be challenging due to their complexity, and the use of modified molecular catalysts may allow us to provide some insight. There are two fundamentally different approaches to understand these important interactions. The "bottom-up" approach involves building an amino acid or peptide containing outer coordination sphere around a functional molecular catalyst, and the "top-down" approach involves attaching molecular catalyst to a structured protein. Both of these approaches have been undertaken for hydrogenase mimics and are the emphasis of this Account. Our focus has been to utilize amino acid or peptide based scaffolds on an active functional enzyme mimic for H2 oxidation and production, [Ni(P(R)2N(R('))2)2](2+). This "bottom-up" approach has allowed us to evaluate individual functional group and structural contributions to electrocatalysts for H2 oxidation and production. For instance, using amine, ether, and carboxylic acid functionalities in the

  5. 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

  6. An e-resource to coordinate research activity with the Readiness for Interprofessional Learning Scale (RIPLS).

    PubMed

    Mattick, Karen; Bligh, John

    2005-12-01

    Research into interprofessional education is often performed by professionals in practice alongside their other "core" duties, thus additional help and support to achieve quality research outcomes would be beneficial. This study aimed to create a virtual community of researchers with shared interest in quantitative studies of interprofessional learning using the Readiness for Interprofessional Learning Scale. An e-resource was built which provided access to relevant resources, helped to coordinate research effort, and promoted communication. Use of the resource was monitored over a 14-month period and evaluated at the end of this time. Forty-eight researchers across six different countries were assigned usernames and passwords. According to a self-report measure, 23/27 (85%) respondents to the evaluation questionnaire had accessed the resource and 95% planned to use it in the coming year. This paper shares our experiences and observations from the study. PMID:16373216

  7. Facile preparation and dual catalytic activity of copper(I)-metallosalen coordination polymers.

    PubMed

    Hou, Yun-Long; Li, Sheng-Xia; Sun, Raymond Wai-Yin; Liu, Xin-Yuan; Weng Ng, Seik; Li, Dan

    2015-10-21

    Three copper(i)-metallosalen coordination polymers (CPs), {[Ni(II)(SalImCy)]2(Cu(I)CN)9}n (1), {[Cu(II)(SalImCy)]2(Cu(I)CN)9}n (2) and {[Ni(II)(SalImCy)](Cu(I)I)2·DMF}n (3) were prepared by direct combination of Ni(II)/Cu(II)(salen) motifs with [Cu(I)CN]n chains and Cu2I2 clusters via the metalloligand strategy. The mixed-valence and mixed-metal CPs could effectively catalyze both the oxidation of aromatic alcohols to ketones and aldehydes under mild conditions and photocatalytic degradation of organic dye methylene blue (MB). This work demonstrates the effective integration of transition metal catalytic Ni(II)/Cu(II)(salen) units and photoactive copper(i) species in a single solid polymer to meet the demand for catalytic materials with the dual catalytic properties. PMID:26388327

  8. Comparison of Cas9 activators in multiple species.

    PubMed

    Chavez, Alejandro; Tuttle, Marcelle; Pruitt, Benjamin W; Ewen-Campen, Ben; Chari, Raj; Ter-Ovanesyan, Dmitry; Haque, Sabina J; Cecchi, Ryan J; Kowal, Emma J K; Buchthal, Joanna; Housden, Benjamin E; Perrimon, Norbert; Collins, James J; Church, George

    2016-07-01

    Several programmable transcription factors exist based on the versatile Cas9 protein, yet their relative potency and effectiveness across various cell types and species remain unexplored. Here, we compare Cas9 activator systems and examine their ability to induce robust gene expression in several human, mouse, and fly cell lines. We also explore the potential for improved activation through the combination of the most potent activator systems, and we assess the role of cooperativity in maximizing gene expression. PMID:27214048

  9. 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

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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

  17. Large roads reduce bat activity across multiple species.

    PubMed

    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

  18. 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

  19. Sudden synchrony leaps accompanied by frequency multiplications in neuronal activity

    PubMed Central

    Vardi, Roni; Goldental, Amir; Guberman, Shoshana; Kalmanovich, Alexander; Marmari, Hagar; Kanter, Ido

    2013-01-01

    A classical view of neural coding relies on temporal firing synchrony among functional groups of neurons, however, the underlying mechanism remains an enigma. Here we experimentally demonstrate a mechanism where time-lags among neuronal spiking leap from several tens of milliseconds to nearly zero-lag synchrony. It also allows sudden leaps out of synchrony, hence forming short epochs of synchrony. Our results are based on an experimental procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in vitro and are corroborated by simulations of neuronal populations. The underlying biological mechanisms are the unavoidable increase of the neuronal response latency to ongoing stimulations and temporal or spatial summation required to generate evoked spikes. These sudden leaps in and out of synchrony may be accompanied by multiplications of the neuronal firing frequency, hence offering reliable information-bearing indicators which may bridge between the two principal neuronal coding paradigms. PMID:24198764

  20. 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

  1. 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

  2. Reactivity of thiosemicarbazides with redox active metal ions: controlled formation of coordination complexes versus heterocyclic compounds.

    PubMed

    López-Torres, Elena; Dilworth, Jonathan R

    2009-01-01

    The reactions of 1,1-dimethyl-4-phenylthiosemicarbazide (LH) with Cu(II) and Sn(IV) have been investigated. If THF or methanol is used as solvent with Cu(II), oxidative cyclisation and coupling are observed, yielding a 1,2,4-thiadiazole or a 1,3,4-thiadiazolium salt. SnI(4) is also able to induce oxidative coupling of two thiosemicarbazide ligands, yielding 1,2,4-thiadiazolium or 1,2,4-triazolium salts, with I(3)(-) as the counterion, depending on the reaction conditions. By contrast, reaction of LH with SnI(4) in acetone yields a 1,3-thiazolium salt, with I(-) as counterion. Reaction with Cu(II) salts or SnI(4) in basic media leads to the formation of metal complexes containing two deprotonated thiosemicarbazide ligands. In the reaction of CuCl(2) in water in the presence of acid a complex containing two neutral ligands is obtained. Reactions with SnCl(4) are not able to induce ligand cyclisation, although a coordination compound with two neutral ligands was isolated from methanol. PMID:19180593

  3. 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.

  4. Unilateral hip osteoarthritis: Its effects on preoperative lower limb muscle activation and intramuscular coordination patterns.

    PubMed

    Schmidt, André; Stief, Felix; Lenarz, Katharina; Froemel, Dara; Lutz, Frederick; Barker, John; Meurer, Andrea

    2016-03-01

    The objective of this study was to test if patients with unilateral hip osteoarthritis (OA) show greater muscle activity asymmetry between their affected and non-affected limbs than healthy controls between their left and right limbs. Seventeen patients with unilateral hip OA (7 females, 10 males) and 17 age-matched healthy controls (7 females, 10 males) participated in this study. Both groups performed instrumented gait analysis at comparable speeds. Muscle activity was recorded simultaneously for the tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST), tensor fasciae latae (TFL), and gluteus medius (GLM) muscles. In hip OA patients, EMG data showed greater activity of the TA muscle in the non-affected limb, and greater TFL muscle activity in the affected limb. Compared to healthy controls, greater asymmetries between paired limbs were observed for the TA and GM muscles. Finally, the TFL muscle of the affected limb contributed more to the total limb muscle activity than did the non-affected limb. The observed alterations in TA and GM muscle activity in hip OA patients may be due to the greater peak braking and peak vertical forces measured in the non-affected limb. Contrary to this, greater TLF muscle activity of the affected limb indicates the demands put on stabilizing the hip during stance phase. Further studies are necessary to test whether leg length discrepancy affects muscle activation alterations between the affected and non-affected limb in unilateral hip OA patients. PMID:26979904

  5. 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. PMID:27154205

  6. Ubiquitin Activates Patatin-Like Phospholipases from Multiple Bacterial Species

    PubMed Central

    Anderson, David M.; Sato, Hiromi; Dirck, Aaron T.; Feix, Jimmy B.

    2014-01-01

    Phospholipase A2 enzymes are ubiquitously distributed throughout the prokaryotic and eukaryotic kingdoms and are utilized in a wide array of cellular processes and physiological and immunological responses. Several patatin-like phospholipase homologs of ExoU from Pseudomonas aeruginosa were selected on the premise that ubiquitin activation of this class of bacterial enzymes was a conserved process. We found that ubiquitin activated all phospholipases tested in both in vitro and in vivo assays via a conserved serine-aspartate catalytic dyad. Ubiquitin chains versus monomeric ubiquitin were superior in inducing catalysis, and ubiquitin-like proteins failed to activate phospholipase activity. Toxicity studies in a prokaryotic dual-expression system grouped the enzymes into high- and low-toxicity classes. Toxicity measured in eukaryotic cells also suggested a two-tiered classification but was not predictive of the severity of cellular damage, suggesting that each enzyme may correspond to unique properties perhaps based on its specific biological function. Additional studies on lipid binding preference suggest that some enzymes in this family may be differentially sensitive to phosphatidyl-4,5-bisphosphate in terms of catalytic activation enhancement and binding affinity. Further analysis of the function and amino acid sequences of this enzyme family may lead to a useful approach to formulating a unifying model of how these phospholipases behave after delivery into the cytoplasmic compartment. PMID:25404699

  7. 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

  8. 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. PMID:25529472

  9. Multiple Intelligences and Positive Life Habits: 174 Activities for Applying Them in Your Classroom.

    ERIC Educational Resources Information Center

    Beachner, Lynne; Pickett, Anola

    This book offers teachers a toolbox for discovering the innate strengths and talents and the unique learning styles of each student. Drawing from Howard Gardner's work on multiple intelligences, the book offers more than a dozen activities specifically tailored to each of the eight multiple intelligences: verbal/linguistic, mathematical/logical,…

  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. Multiple-Coincidence Active Neutron Interrogation of Fissionable Materials

    SciTech Connect

    Tinsley, J.R., Hurley, J.P., Trainham, R., Keegan, R.P.

    2008-11-14

    In an extension of the Associated Particle Imaging technique that is used for the detection and imaging of hidden explosives, the present measurements use a beam of tagged 14.1 MeV neutrons in coincidence with two or more gammas to probe for the presence of fissionable materials. We have measured neutron-gamma-gamma coincidences with targets of depleted uranium, tungsten, lead, iron, and carbon and will present results that show the multiple-coincidence counting rate for the depleted uranium is substantially higher than any of the non-fissionable materials. In addition, the presence of coincidences involving delayed particle spectra provides a signature for fissionable materials that is distinct from that for non-fissionable ones. Information from the tagged neutron involved in the coincidence event is used to compute the position of the fissionable material in all three dimensions. The result is an imaging probe for fissionable materials that is compact and portable, and produces relatively low levels of background radiation. Simultaneous measurements on packages of interest for both explosives and fissionable materials are now feasible.

  12. Upper extremity coordination strategies depending on task demand during a basic daily activity.

    PubMed

    Ricci, Flávia Pessoni F M; Santiago, Paulo Roberto Pereira; Zampar, Ana Carolina; Pinola, Lívia Nahas; Fonseca, Marisa de Cássia Registro

    2015-10-01

    Injury conditions affecting the upper extremity may lead to severe functional impairment and an accurate evaluation is needed in order to select the most effective treatment in a rehabilitation program. This study focused on simultaneous electromyographic and kinematic analysis to assess movement patterns of upper extremity during a basic daily activity, considering different demands existing within the task. Twenty-five healthy subjects, average age 19.8 ys SD 1.7 ys, with no upper extremity impairment, were assessed by means of electromyography (EMG) and a 3D motion capture system while performing a task that required reach, transport and release. Integrated EMG (iEMG), timing of muscle onset and active range of motion (AROM) were calculated for each subject. Data were compared within each phase and between the three phases and a repeated measure ANOVA was used for statistical analysis. We found early activation of upper trapezius associated with high activity of serratus anterior for proximal stability while anterior deltoid and triceps brachii performed shoulder flexion and elbow extension, in Reach phase. In Transport phase there was early and higher activation of upper trapezius, higher muscle activity of almost all muscles and increased AROM of all joints. No change in flexion/extension wrist posture with increased forearm muscles activity were identified as the main control strategy to keep optimal grasping. Triceps brachii was found to act as an important synergist in shoulder abduction and extension in free load conditions. Such information can lead clinicians to more specific assessment and subsequent better intervention in upper extremity rehabilitation. PMID:26282047

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

    Energy Science and Technology Software Center (ESTSC)

    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. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Linking of trinuclear pivalate Fe2NiO(Piv)6 (Piv=O2CC(CH3)3) by 2,6-bis(4-pyridyl)-4-(1-naphthyl)pyridine (L) resulted in formation of 1D-porous coordination polymer Fe2NiO(Piv)6(L)·Solv, which was characterized in two forms: DMSO solvate Fe2NiO(Piv)6(L)(DMSO)·2.5DMSO (1) or water solvate Fe2NiO(Piv)6(L)(H2O) (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 Fe2NiO(Piv)6(L) was confirmed by the measurements of N2 and H2 adsorption at 77 K. Potential barriers of the different molecules diffusion through pores were estimated by the means of molecular mechanics.

  16. 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

  17. 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…

  18. 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.

  19. 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. PMID:26037052

  20. ACT-Vision: active collaborative tracking for multiple PTZ cameras

    NASA Astrophysics Data System (ADS)

    Broaddus, Christopher; Germano, Thomas; Vandervalk, Nicholas; Divakaran, Ajay; Wu, Shunguang; Sawhney, Harpreet

    2009-04-01

    We describe a novel scalable approach for the management of a large number of Pan-Tilt-Zoom (PTZ) cameras deployed outdoors for persistent tracking of humans and vehicles, without resorting to the large fields of view of associated static cameras. Our system, Active Collaborative Tracking - Vision (ACT-Vision), is essentially a real-time operating system that can control hundreds of PTZ cameras to ensure uninterrupted tracking of target objects while maintaining image quality and coverage of all targets using a minimal number of sensors. The system ensures the visibility of targets between PTZ cameras by using criteria such as distance from sensor and occlusion.

  1. The Structure of Sec12 Implicates Potassium Ion Coordination in Sar1 Activation*

    PubMed Central

    McMahon, Conor; Studer, Sean M.; Clendinen, Chaevia; Dann, Geoffrey P.; Jeffrey, Philip D.; Hughson, Frederick M.

    2012-01-01

    Coat protein II (COPII)-coated vesicles transport proteins and lipids from the endoplasmic reticulum to the Golgi. Crucial for the initiation of COPII coat assembly is Sec12, a guanine nucleotide exchange factor responsible for activating the small G protein Sar1. Once activated, Sar1/GTP binds to endoplasmic reticulum membranes and recruits COPII coat components (Sec23/24 and Sec13/31). Here, we report the 1.36 Å resolution crystal structure of the catalytically active, 38-kDa cytoplasmic portion of Saccharomyces cerevisiae Sec12. Sec12 adopts a β propeller fold. Conserved residues cluster around a loop we term the “K loop,” which extends from the N-terminal propeller blade. Structure-guided site-directed mutagenesis, in conjunction with in vitro and in vivo functional studies, reveals that this region of Sec12 is catalytically essential, presumably because it makes direct contact with Sar1. Strikingly, the crystal structure also reveals that a single potassium ion stabilizes the K loop; bound potassium is, moreover, essential for optimum guanine nucleotide exchange activity in vitro. Thus, our results reveal a novel role for a potassium-stabilized loop in catalyzing guanine nucleotide exchange. PMID:23109340

  2. Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death.

    PubMed

    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

    2013-11-01

    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

  3. 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

  4. 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

  5. Coordination changes and auto-hydroxylation of FIH-1: uncoupled O2-activation in a human hypoxia sensor

    PubMed Central

    Chen, Yuan-Han; Comeaux, Lindsay M.; Herbst, Robert W.; Saban, Evren; Kennedy, David C.; Maroney, Michael J.; Knapp, Michael J.

    2008-01-01

    Hypoxia sensing is the generic term for pO2-sensing in humans and other higher organisms. These cellular responses to pO2 are largely controlled by enzymes that belong to the Fe(II) α-ketoglutarate (αKG) dependent dioxygenase superfamily, including the human enzyme called the Factor Inhibiting HIF (FIH-1), which couples O2-activation to the hydroxylation of the Hypoxia Inducible Factor α (HIFα). Uncoupled O2-activation by human FIH-1 was studied by exposing the resting form of FIH-1, (αKG+Fe)FIH-1, to air in the absence of HIFα. Uncoupling lead to two distinct enzyme oxidations, one a purple chromophore (λmax = 583 nm) arising from enzyme auto-hydroxylation of Trp296, forming an Fe(III)–O–Trp296 chromophore (Y.-H. Chen, L. M. Comeaux, S. J. Eyles, M. J. Knapp, Chem. Commun. (2008) DOI:10.1039/B809099H); the other a yellow chromophore due to Fe(III) in the active site, which under some conditions also contained variable levels of an oxygenated surface residue, (oxo)Met275. The kinetics of purple FIH-1 formation were independent of Fe(II) and αKG concentrations, however product yield was saturable with increasing [αKG] and required excess Fe(II). Yellow FIH-1 was formed from (succinate+Fe)FIH-1, or by glycerol addition to (αKG+Fe)FIH-1, suggesting that glycerol could intercept the active oxidant from the FIH-1 active site and prevent hydroxylation. Both purple and yellow FIH-1 contained high-spin, rhombic Fe(III) centers, as shown by low temperature EPR. XAS indicated distorted octahedral Fe(III) geometries, with subtle differences in inner-shell ligands for yellow and purple FIH-1. EPR of Co(II)-substituted FIH-1, (αKG+Co)FIH-1, indicated a mixture of 5-coordinate and 6-coordinate enzyme forms, suggesting that resting FIH-1 can readily undergo uncoupled O2-activation by loss of an H2O ligand from the metal center. PMID:18805587

  6. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    PubMed Central

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed. PMID:26618142

  7. 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

  8. 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

  9. 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)

  10. 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

  11. 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

  12. 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

  13. Coordinate Control of Muscle Cell Survival by Distinct Insulin-like Growth Factor Activated Signaling Pathways

    PubMed Central

    Lawlor, Margaret A.; Rotwein, Peter

    2000-01-01

    Peptide growth factors control diverse cellular functions by regulating distinct signal transduction pathways. In cultured myoblasts, insulin-like growth factors (IGFs) stimulate differentiation and promote hypertrophy. IGFs also maintain muscle cell viability. We previously described C2 skeletal muscle lines lacking expression of IGF-II. These cells did not differentiate, but underwent progressive apoptotic death when incubated in differentiation medium. Viability could be sustained and differentiation enabled by IGF analogues that activated the IGF-I receptor; survival was dependent on stimulation of phosphatidylinositol 3-kinase (PI3-kinase). We now find that IGF action promotes myoblast survival through two distinguishable PI3-kinase–regulated pathways that culminate in expression of the cyclin-dependent kinase inhibitor, p21. Incubation with IGF-I or transfection with active PI3-kinase led to rapid induction of MyoD and p21, and forced expression of either protein maintained viability in the absence of growth factors. Ectopic expression of MyoD induced p21, and inhibition of p21 blocked MyoD-mediated survival, thus defining one PI3-kinase–dependent pathway as leading first to MyoD, and then to p21 and survival. Unexpectedly, loss of MyoD expression did not impede IGF-mediated survival, revealing a second pathway involving activation by PI3-kinase of Akt, and subsequent induction of p21. Since inhibition of p21 caused death even in the presence of IGF-I, these results establish a central role for p21 as a survival factor for muscle cells. Our observations also define a MyoD-independent pathway for regulating p21 in muscle, and demonstrate that distinct mechanisms help ensure appropriate expression of this key protein during differentiation. PMID:11121430

  14. 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.

  15. 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.

  16. Multiplicative and Additive Modulation of Neuronal Tuning with Population Activity Affects Encoded Information.

    PubMed

    Arandia-Romero, Iñigo; Tanabe, Seiji; Drugowitsch, Jan; Kohn, Adam; Moreno-Bote, Rubén

    2016-03-16

    Numerous studies have shown that neuronal responses are modulated by stimulus properties and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation and vice versa. The information encoded by multiplicatively modulated neurons increased with greater population activity, while that of additively modulated neurons decreased. These effects offset each other so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a "traffic light" that determines which subset of neurons is most informative. PMID:26924437

  17. The SUMO E3 ligase activity of Pc2 is coordinated through a SUMO interaction motif.

    PubMed

    Yang, Shen-hsi; Sharrocks, Andrew D

    2010-05-01

    Protein modification by SUMO conjugation has emerged to be an important regulatory event. Recently, the mechanisms through which SUMO elicits its effects on target proteins have been elucidated. One of these is the noncovalent association between SUMO and coregulatory proteins via SUMO interaction motifs (SIMs). We therefore searched for additional binding proteins to elucidate how SUMO acts as a signal to potentiate novel noncovalent interactions with SUMO-binding proteins. We identified an E3 ligase, Pc2, as a SUMO-binding protein with two functionally distinct SIMs. Here, we focus on the role of SIM2 and demonstrate that it is crucial for many of the documented Pc2 functions, which converge on determining its E3 ligase activity. One role of SUMO binding in this context is the subnuclear partitioning of the active form of Ubc9 (SUMO approximately Ubc9) by Pc2. The significance of the SIM2-dependent functions of Pc2 is demonstrated in the control of the precise expression of lineage-specific genes during embryonic stem cell differentiation. PMID:20176810

  18. Perceived athletic competence and physical activity in children with developmental coordination disorder who are clinically referred, and control children.

    PubMed

    Noordstar, Johannes J; Stuive, Ilse; Herweijer, Hester; Holty, Lian; Oudenampsen, Chantal; Schoemaker, Marina M; Reinders-Messelink, Heleen A

    2014-12-01

    The relationship between perceived athletic competence (PAC) and physical activity (PA) in children with developmental coordination disorder (DCD) is still unclear. This study investigated differences in PAC and PA between, and within, a group of children with DCD that were clinically referred (n = 31) and a group of control children (n = 38), aged 7-12 years. All children were categorized in four groups: (1) children with DCD/low PAC, (2) children with DCD/normal to high PAC, (3) control children/low PAC, and (4) control children/normal to high PAC. PAC was assessed with the Self-Perception Profile for Children, and PA was assessed with the Modifiable Activity Questionnaire. Children with DCD participated less in unorganized PA, but not in organized PA, compared with control children. Normal to high PAC was found in more than half of the children (64.5%) with DCD. Children with DCD/low PAC and children with DCD/normal to high PAC participated significantly less in unorganized physical activity compared with control children/normal to high PAC, but not compared with control children/low PAC. The results indicate that there are large individual differences in PAC in children with DCD. PMID:25244693

  19. Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol.

    PubMed

    Gutierrez-Uzquiza, Alvaro; Colon-Gonzalez, Francheska; Leonard, Thomas A; Canagarajah, Bertram J; Wang, HongBin; Mayer, Bruce J; Hurley, James H; Kazanietz, Marcelo G

    2013-01-01

    Chimaerins, a family of GTPase activating proteins for the small G-protein Rac, have been implicated in development, neuritogenesis and cancer. These Rac-GTPase activating proteins are regulated by the lipid second messenger diacylglycerol generated by tyrosine kinases such as the epidermal growth factor receptor. Here we identify an atypical proline-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. Epidermal growth factor promotes the binding of β2-chimaerin to Nck1 in the cell periphery in a diacylglycerol-dependent manner. Moreover, β2-chimaerin translocation to the plasma membrane and its peripheral association with Rac1 requires Nck1. Our studies underscore a coordinated mechanism for β2-chimaerin activation that involves lipid interactions via the C1 domain and protein-protein interactions via the N-terminal proline-rich region. PMID:23673634

  20. Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development.

    PubMed

    Luo, Wen; Zhao, Xia; Jin, Hengwei; Tao, Lichan; Zhu, Jingai; Wang, Huijuan; Hemmings, Brian A; Yang, Zhongzhou

    2015-02-15

    Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract. Cell proliferation of cardiac progenitors was enhanced, whereas cardiac differentiation was unaffected by Pten deletion. Removal of Akt1 rescued the phenotype and early lethality of Pten deletion mice, suggesting that Akt1 was the key downstream target that was negatively regulated by PTEN in cardiac progenitors. Furthermore, we found that inhibition of FOXO by Akt1 suppressed the expression of the gene encoding the BMP ligand (BMP7), leading to dampened BMP signaling in the hearts of Pten deletion mice. Cardiac activation of Akt also increased the Ser552 phosphorylation of β-catenin, thus enhancing its activity. Reducing β-catenin levels could partially rescue heart defects of Pten deletion mice. We conclude that Akt signaling regulates the cell proliferation of SHF progenitors through coordination of BMP signaling and β-catenin activity. PMID:25670795

  1. 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

  2. A self-centering active probing technique for kinematic parameter identification and verification of articulated arm coordinate measuring machines

    NASA Astrophysics Data System (ADS)

    Santolaria, J.; Brau, A.; Velázquez, J.; Aguilar, J. J.

    2010-05-01

    A crucial task in the procedure of identifying the parameters of a kinematic model of an articulated arm coordinate measuring machine (AACMM) or robot arm is the process of capturing data. In this paper a capturing data method is analyzed using a self-centering active probe, which drastically reduces the capture time and the required number of positions of the gauge as compared to the usual standard and manufacturer methods. The mathematical models of the self-centering active probe and AACMM are explained, as well as the mathematical model that links the AACMM global reference system to the probe reference system. We present a self-calibration method that will allow us to determine a homogeneous transformation matrix that relates the probe's reference system to the AACMM last reference system from the probing of a single sphere. In addition, a comparison between a self-centering passive probe and self-centering active probe is carried out to show the advantages of the latter in the procedures of kinematic parameter identification and verification of the AACMM.

  3. Evaluating Physical Activity Using Accelerometry in Children at Risk of Developmental Coordination Disorder in the Presence of Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Baerg, Sally; Cairney, John; Hay, John; Rempel, Lynn; Mahlberg, Nadilein; Faught, Brent E.

    2011-01-01

    Physical activity (PA) is compromised in children and adolescents with developmental coordination disorder (DCD). Approximately half of all children with DCD suffer from attention-deficit hyperactive disorder (ADHD); a cohort often considered more physically active than typically developing youth. Accelerometry is an effective method of assessing…

  4. Nuclear envelope lamin-A as a coordinator of T cell activation

    PubMed Central

    Rocha-Perugini, Vera; González-Granado, José M

    2014-01-01

    Nuclear lamins A/C control several critical cellular functions, e.g., chromatin organization, gene transcription, DNA replication, DNA damage responses, cell cycle progression, cell differentiation, and cell polarization during migration. However, few studies have addressed the role of lamins A/C in the control of the functions of immune cells. Recently, we have demonstrated that lamins A/C are induced in T cells upon antigen recognition. Lamins A/C enhance T cell responses by coupling the plasma membrane to the nucleus via the linker of nucleoskeleton and cytoskeleton (LINC) complex and the actin cytoskeleton. Here, we discuss the possible physiological relevance and functional context of lamin A/C in T cell activation and propose a model in which lamins A/C are key modulators of immune cell functions. PMID:25482193

  5. Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets

    PubMed Central

    Rocheleau, Jonathan V.; Walker, Glenn M.; Head, W. Steven; McGuinness, Owen P.; Piston, David W.

    2004-01-01

    The pancreatic islet is a functional microorgan involved in maintaining normoglycemia through regulated secretion of insulin and other hormones. Extracellular glucose stimulates insulin secretion from islet β cells through an increase in redox state, which can be measured by NAD(P)H autofluorescence. Glucose concentrations over ≈7 mM generate synchronous oscillations in β cell intracellular Ca2+ concentration ([Ca2+]i), which lead to pulsatile insulin secretion. Prevailing models assume that the pancreatic islet acts as a functional syncytium, and the whole islet [Ca2+]i response has been modeled in terms of islet bursting and pacemaker models. To test these models, we developed a microfluidic device capable of partially stimulating an islet, while allowing observation of the NAD(P)H and [Ca2+]i responses. We show that β cell [Ca2+]i oscillations occur only within regions stimulated with more than ≈6.6 mM glucose. Furthermore, we show that tolbutamide, an antagonist of the ATP-sensitive K+ channel, allows these oscillations to travel farther into the nonstimulated regions of the islet. Our approach shows that the extent of Ca2+ propagation across the islet depends on a delicate interaction between the degree of coupling and the extent of ATP-sensitive K+-channel activation and illustrates an experimental paradigm that will have utility for many other biological systems. PMID:15317941

  6. 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

  7. 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

  8. A shared mechanism for lipid- and β-subunit-coordinated stabilization of the activated K+ channel voltage sensor

    PubMed Central

    Choi, Eun; Abbott, Geoffrey W.

    2010-01-01

    The low-dielectric plasma membrane provides an energy barrier hindering transmembrane movement of charged particles. The positively charged, voltage-sensing fourth transmembrane domain (S4) of voltage-gated ion channels must surmount this energy barrier to initiate channel activation, typically necessitating both membrane depolarization and interaction with membrane lipid phospho-head groups (MLPHGs). In contrast, and despite containing S4, the KCNQ1 K+ channel α subunit exhibits predominantly constitutive activation when in complexes with transmembrane β subunits, MinK-related peptide (MiRP) 1 (KCNE2) or MiRP2 (KCNE3). Here, using a 2-electrode voltage clamp and scanning mutagenesis of channels heterologously expressed in Xenopus laevis oocytes, we discovered that 2 of the 8 MiRP2 extracellular domain acidic residues (D54 and D55) are important for KCNQ1-MiRP2 constitutive activation. Double-mutant thermodynamic cycle analysis revealed energetic coupling of D54 and D55 to R237 in KCNQ1 S4 but not to 10 other native or introduced polar residues in KCNQ1 S4 and surrounding linkers. MiRP2-D54 and KCNQ1-R237 also similarly dictated susceptibility to the inhibitory effects of MLPHG hydrolysis, whereas other closely situated polar residues did not. Thus, by providing negative charge near the plasma membrane extracellular face, MiRP2 uses a lipomimetic mechanism to constitutively stabilize the activated KCNQ1 voltage sensor.—Choi, E., Abbott, G. W. A shared mechanism for lipid- and β-subunit-coordinated stabilization of the activated K+ channel voltage sensor. PMID:20040519

  9. 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).…

  10. 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…

  11. 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…

  12. Individual Focus in an Activity Centre: An Observational Study among Persons with Profound and Multiple Disabilities

    ERIC Educational Resources Information Center

    Hiemstra, S. J.; Vlaskamp, C.; Wiersma, L. A.

    2007-01-01

    Increasing numbers of adults with profound intellectual and multiple disabilities (PIMD) are being offered more--and more frequent--day services at activity centres. Little is known about the way direct support persons (DSP) in activity centres divide their time over the various tasks they have to perform and to what extent they are focused on…

  13. 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

  14. Differential downregulation of telomerase activity by bortezomib in multiple myeloma cells-multiple regulatory pathways in vitro and ex vivo

    PubMed Central

    Weiss, C; Uziel, O; Wolach, O; Nordenberg, J; Beery, E; Bulvick, S; Kanfer, G; Cohen, O; Ram, R; Bakhanashvili, M; Magen-Nativ, H; Shilo, N; Lahav, M

    2012-01-01

    Background: The importance of telomerase in multiple myeloma (MM) is well established; however, its response to bortezomib has not been addressed. Methods: The effect of bortezomib on telomerase activity and cell proliferation was evaluated in four MM cell lines and in myeloma cells obtained from eight patients. The mechanism of telomerase regulation on epigenetic, transcriptional, and post-translational levels was further assessed in two selected cell lines: ARP-1 and CAG. Clinical data were correlated with the laboratory findings. Results: Bortezomib downregulated telomerase activity and decreased proliferation in all cell lines and cells obtained from patients, albeit in two different patterns of kinetics. ARP-1 cells demonstrated higher and earlier sensitivity than CAG cells due to differential phosphorylation of hTERT by PKCα. Methylation of hTERT promoter was not affected. Transcription of hTERT was similarly inhibited in both lines by decreased binding of SP-1 and not of C-Myc and NFκB. The ex vivo results confirmed the in vitro findings and suggested existence of clinical relevance. Conclusion: Bortezomib downregulates telomerase activity in MM cells both transcriptionally and post-translationally. MM cells, both in vitro and in patients, exhibit different sensitivity to the drug due to different post-translational response. The effect of bortezomib on telomerase activity may correlate with resistance to bortezomib in patients, suggesting its potential utility as a pre-treatment assessment. PMID:23169337

  15. 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)

  16. 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.

  17. FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2

    PubMed Central

    Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

    2015-01-01

    How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth. PMID:26632449

  18. Longitudinal analysis of motor activity and coordination, anxiety, and spatial learning in mice with altered blood pressure.

    PubMed

    Thifault, S; Lalonde, R; Sanon, N; Hamet, P

    2001-08-10

    Mice with either high or low blood pressure (BP) were compared to normotensive controls at 2 and 12 months of age for motor activity, equilibrium, anxiety, and spatial learning. Irrespective of age, high BP mice were more active in an open field than normotensive controls, whereas low BP mice were hypoactive at 2 months of age. High BP mice had a higher number of entries and a longer duration of visits in the open arms, a higher open arm/total arm ratio, a longer duration for the first visit into an open arm, and lower latencies before entering the first open arm than controls in the elevated +-maze, indicative of reduced anxiety. Reduced levels of anxiety were also displayed by low BP mice for the duration of the first open arm visit (both age groups) and for the time spent in the open arms (older group). In the motor coordination test (coat-hanger), high BP mice had higher two-paw movement time and reached the top of the apparatus on fewer occasions than controls. Both groups with abnormal BP values were deficient during visuomotor guidance in the water maze. These results indicate strain-, age-, and test-specific abnormalities in mice with uncontrolled hypertension or hypotension. PMID:11489259

  19. 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

  20. 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.

  1. 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.

  2. FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2.

    PubMed

    Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

    2015-01-01

    How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth. PMID:26632449

  3. Mononuclear and dinuclear peroxotungsten complexes with co-ordinated dipeptides as potent inhibitors of alkaline phosphatase activity.

    PubMed

    Hazarika, Pankaj; Kalita, Diganta; Islam, Nashreen S

    2008-08-01

    New molecular peroxotungstate(VI) complexes with dipeptides as ancillary ligands of the type, [WO(O(2))(2)(dipeptide)(H(2)O)].3H(2)O, dipeptide = glycyl-glycine or glycyl-leucine, have been synthesized and characterized by elemental analysis, spectral and physico-chemical methods including thermal analysis. The complexes contain side-on bound peroxo groups and a peptide zwitterion bonded to the metal centre unidentately through an O(carboxylate) atom. Investigations on certain biologically important key properties of these compounds and a set of dimeric compounds in analogous co-ligand environment, Na(2)[W(2)O(3)(O(2))(4)(dipeptide)(2)].3H(2)O, dipeptide = glycyl-glycine and glycyl-leucine, reported previously by us revealed interesting features of the compounds. Each of the compounds despite having a 7 co-ordinated metal centre exerts a strong inhibitory effect on alkaline phosphatase activity with a potency higher than that of the free dipeptide, tungstate or peroxotungstate. The compounds exhibit remarkable stability in solutions of acidic as well as physiological pH and are weaker as substrate to the enzyme catalase, compared to H(2)O(2). The mononuclear and dinuclear peroxotungsten compounds are efficient oxidants of reduced glutathione (GSH), a reaction in which only one of the peroxo groups of a diperoxotungsten moiety of the complexes was found to be active. PMID:18665997

  4. Care Coordination for the Chronically Ill: Understanding the Patient's Perspective

    PubMed Central

    Maeng, Daniel D; Martsolf, Grant R; Scanlon, Dennis P; Christianson, Jon B

    2012-01-01

    Objective To identify factors associated with perception of care coordination problems among chronically ill patients. Methods Patient-level data were obtained from a random-digit dial telephone survey of adults with chronic conditions. The survey measured respondents' self-report of care coordination problems and level of patient activation, using the Patient Activation Measure (PAM-13). Logistic regression was used to assess association between respondents' self-report of care coordination problems and a set of patient characteristics. Results Respondents in the highest activation stage had roughly 30–40 percent lower odds of reporting care coordination problems compared to those in the lowest stage (p < .01). Respondents with multiple chronic conditions were significantly more likely to report coordination problems than those with hypertension only. Respondents' race/ethnicity, employment, insurance status, income, and length of illness were not significantly associated with self-reported care coordination problems. Conclusion We conclude that patient activation and complexity of chronic illness are strongly associated with patients' self-report of care coordination problems. Developing targeted strategies to improve care coordination around these patient characteristics may be an effective way to address the issue. PMID:22985032

  5. Coordinate activation of lysosomal, Ca 2+-activated and ATP-ubiquitin-dependent proteinases in the unweighted rat soleus muscle.

    PubMed Central

    Taillandier, D; Aurousseau, E; Meynial-Denis, D; Bechet, D; Ferrara, M; Cottin, P; Ducastaing, A; Bigard, X; Guezennec, C Y; Schmid, H P

    1996-01-01

    Nine days of hindlimb suspension resulted in atrophy (55%) and loss of protein (53%) in rat soleus muscle due to a marked elevation in protein breakdown (66%, P < 0.005). To define which proteolytic system(s) contributed to this increase, soleus muscles from unweighted rats were incubated in the presence of proteolytic inhibitors. An increase in lysosomal and Ca 2+-activated proteolysis (254%, P < 0.05) occurred in the atrophying incubated muscles. In agreement with the measurements in vitro, cathepsin B, cathepsins B + L and m-calpain enzyme activities increased by 111%, 92% and 180% (P < 0.005) respectively in the atrophying muscles. Enhanced mRNA levels for these proteinases (P < 0.05 to P < 0.001) paralleled the increased enzyme activities, suggesting a transcriptional regulation of these enzymes. However, the lysosomal and Ca 2+-dependent proteolytic pathways accounted for a minor part of total proteolysis in both control (9%) and unweighted rats (18%). Furthermore the inhibition of these pathways failed to suppress increased protein breakdown in unweighted muscle. Thus a non-lysosomal Ca 2+-independent proteolytic process essentially accounted for the increased proteolysis and subsequent muscle wasting. Increased mRNA levels for ubiquitin, the 14 kDa ubiquitin-conjugating enzyme E2 (involved in the ubiquitylation of protein substrates) and the C2 and C9 subunits of the 20 S proteasome (i.e. the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates) were observed in the atrophying muscles (P < 0.02 to P < 0.001). Analysis of C9 mRNA in polyribosomes showed equal distribution into both translationally active and inactive mRNA pools, in either unweighted or control rats. These results suggest that increased ATP-ubiquitin-dependent proteolysis is most probably responsible for muscle wasting in the unweighted soleus muscle. PMID:8645234

  6. 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.

  7. 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.

  8. 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.

  9. 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. PMID:24785803

  10. 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. PMID:26595361

  11. An Integrated Children's Mental Health System: Coordinating the Needs of Children with Multiple Problems: Children's Integrated Fund Task Force Report to the Minnesota Legislature..

    ERIC Educational Resources Information Center

    Cox, Gary C.

    This report proposes creation of a flexible and coordinated system for delivery of comprehensive community-based services to Minnesota children with emotional and behavioral disorders. The proposal calls for the state to support multiagency Local Collaboratives with: (1) legislation that grants local communities certain powers in exchange for…

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Hybrid coordination-network-engineering for bridging cascaded channels to activate long persistent phosphorescence in the second biological window.

    PubMed

    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 Nd(3+) and Cr(3+). 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

  17. 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

  18. 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

  19. 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

    2013-01-01

    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

  20. Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey

    PubMed Central

    2014-01-01

    Background There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. Methods The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey – Revised, Exercise Self-Efficacy Scale, Falls- Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Results Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Conclusions Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active. PMID:24612446

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. Normal shoulder muscular activation and co-ordination during a shoulder elevation task based on activities of daily living: an electromyographic study.

    PubMed

    Hawkes, David H; Alizadehkhaiyat, Omid; Fisher, Anthony C; Kemp, Graham J; Roebuck, Margaret M; Frostick, Simon P

    2012-01-01

    Studies of normal shoulder function have often failed to consider the inter-relationship between different muscle groups in activities relevant to daily life. Upper limb functional status was assessed in 12 healthy male volunteers using the Functional Impairment Test-Hand, Neck, Shoulder and Arm test (FIT-HaNSA). Electromyography was then used to study the activity and coordination of 13 muscles (10 by surface electrodes, 3 by fine-wire intramuscular electrodes) around the shoulder during a dynamic movement task based on the shelf-lifting task in FIT-HaNSA. Muscles were grouped for analysis into deltoid (anterior, middle, and posterior divisions), adductors (latissimus dorsi and teres major), rotator cuff (supraspinatus, infraspinatus, and subscapularis), and elbow flexor (brachioradialis, biceps brachii) groups. There were no significant inter-session effects. Using cross-correlation analysis to investigate the whole time-course of activation, there were highly significant positive correlations (p < 0.001) between the deltoid and rotator cuff, the deltoid and adductor and the adductor and rotator cuff groups, and a significant negative correlation between the deltoid and elbow flexor groups (p = 0.031). We conclude that the deltoid, adductor, and rotator cuff muscles all contribute to the muscular component of glenohumeral joint stability. Muscular stability can be adapted as required to meet task-specific demands. PMID:21674607

  6. 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. PMID:23337502

  7. 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. PMID:26386431

  8. Magnetosheath Coordinates

    NASA Astrophysics Data System (ADS)

    Schulz, M.; Chen, M. W.

    2010-12-01

    The eventual goal of this work is to develop an approximate analytical representation of solar-wind streamlines in the magnetosheath surrounding a magnetosphere of rather general shape. Previous analytical representations of magnetosheath streamlines and magnetic fields have invoked magnetopause shapes that conform to standard coordinate systems (e.g., spherical, cylindrical, paraboloidal, ellipsoidal), but it seems now that such a restriction on magnetopause shape is unnecessary. In the present work it is assumed only that the magnetopause is a continuously differentiable convex surface axisymmetric about the Sun-Earth line. This geometry permits the construction of an orthogonal coordinate system (mu, eta, chi) such that eta is the cosine of the cone angle between the Sun-Earth line and any conical surafce extending normally outward from the magnetopause, mu is a measure of the perpendicular distance of any magnetosheath point from the magnetopause, and chi is an azimuthal coordinate measured around the Sun-Earth line. It is convenient here to assign a label mu = mu* to the magnetopause itself, so that mu - mu* denotes perpendicular distance from the magnetopause and mu* is an adjustable parameter roughly comparable to the radius of the magnetotail. This choice provides for a rough correspondence between the (mu, eta, chi) coordinates introduced here and the ellipsoidal coordinates used in our previous efforts at magnetosheath modeling.

  9. 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…

  10. 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.

  11. ∆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

  12. 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

  13. Promiscuous Mutations Activate the Non-Canonical NF-kB Pathway in Multiple Myeloma

    PubMed Central

    Keats, Jonathan J.; Fonseca, Rafael; Chesi, Marta; Schop, Roelandt; Baker, Angela; Chng, Wee-Joo; Van Wier, Scott; Tiedemann, Rodger; Shi, Chang-Xin; Sebag, Michael; Braggio, Esteban; Henry, Travis; Zhu, Yuan-Xiao; Fogle, Homer; Price-Troska, Tammy; Ahmann, Gregory; Mancini, Catherine; Brents, Leslie A.; Kumar, Shaji; Greipp, Philip; Dispenzieri, Angela; Bryant, Barb; Mulligan, George; Bruhn, Laurakay; Barrett, Michael; Valdez, Riccardo; Trent, Jeff; Stewart, A. Keith; Carpten, John; Bergsagel, P. Leif

    2007-01-01

    Summary Activation of NF-kB has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-kB in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2, and activation of NFKB1, NFKB2, CD40, LTBR, TACI, and NIK that result primarily in constitutive activation of the non-canonical NF-kB pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-kB pathway in the pathogenesis of multiple myeloma. PMID:17692805

  14. 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

  15. Activity Monitoring and Motion Classification of the Lizard Chamaeleo jacksonii Using Multiple Doppler Radars

    PubMed Central

    Singh, Aditya; Lee, Scott SK; Butler, Marguerite; Lubecke, Victor

    2016-01-01

    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

  16. 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.

  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. 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. Effects of hydrogen sulfide on the heme coordination structure and catalytic activity of the globin-coupled oxygen sensor AfGcHK.

    PubMed

    Fojtikova, Veronika; Bartosova, Martina; Man, Petr; Stranava, Martin; Shimizu, Toru; Martinkova, Marketa

    2016-08-01

    AfGcHK is a globin-coupled histidine kinase that is one component of a two-component signal transduction system. The catalytic activity of this heme-based oxygen sensor is due to its C-terminal kinase domain and is strongly stimulated by the binding of O2 or CO to the heme Fe(II) complex in the N-terminal oxygen sensing domain. Hydrogen sulfide (H2S) is an important gaseous signaling molecule and can serve as a heme axial ligand, but its interactions with heme-based oxygen sensors have not been studied as extensively as those of O2, CO, and NO. To address this knowledge gap, we investigated the effects of H2S binding on the heme coordination structure and catalytic activity of wild-type AfGcHK and mutants in which residues at the putative O2-binding site (Tyr45) or the heme distal side (Leu68) were substituted. Adding Na2S to the initial OH-bound 6-coordinate Fe(III) low-spin complexes transformed them into SH-bound 6-coordinate Fe(III) low-spin complexes. The Leu68 mutants also formed a small proportion of verdoheme under these conditions. Conversely, when the heme-based oxygen sensor EcDOS was treated with Na2S, the initially formed Fe(III)-SH heme complex was quickly converted into Fe(II) and Fe(II)-O2 complexes. Interestingly, the autophosphorylation activity of the heme Fe(III)-SH complex was not significantly different from the maximal enzyme activity of AfGcHK (containing the heme Fe(III)-OH complex), whereas in the case of EcDOS the changes in coordination caused by Na2S treatment led to remarkable increases in catalytic activity. PMID:27395436

  20. 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

  1. Most Common Types of Physical Activity Self-Selected by People with Multiple Sclerosis

    PubMed Central

    Weikert, Madeline; Dlugonski, Deirdre; Balantrapu, Swathi

    2011-01-01

    The promotion of physical activity for people with multiple sclerosis (MS) would benefit from information about the common types of physical activity self-selected by this population. This study examined the most frequent types of physical activity self-reported by a large sample of people with MS. The data were collected as part of the baseline assessment of a longitudinal investigation of physical activity in relapsing-remitting MS (RRMS). The participants (N = 272) were sent a battery of questionnaires through the US Postal Service that included the Modifiable Activity Questionnaire for assessing types of physical activity performed during the previous year. Walking was ranked number 1 for both the first and second most common types of physical activity self-selected by people with MS, and it was ranked number 4 as the third most common type of self-selected physical activity. Collectively, 79% of the sample reported walking as a frequent form of self-selected physical activity in the previous year. Other notable types of physical activities self-selected by people with MS were gardening (44%), weight training (34%), bicycling (30%), and calisthenics (20%). This information may assist clinicians and practitioners in the development of physical activity programs and recommendations for people with MS. PMID:24453701

  2. B═B and B≡E (E = N and o) multiple bonds in the coordination sphere of late transition metals.

    PubMed

    Brand, Johannes; Braunschweig, Holger; Sen, Sakya S

    2014-01-21

    Because of their unusual structural and bonding motifs, multiply bonded boron compounds are fundamentally important to chemists, leading to enormous research interest. To access these compounds, researchers have introduced sterically demanding ligands that provide kinetic as well as electronic stability. A conceptually different approach to the synthesis of such compounds involves the use of an electron-rich, coordinatively unsaturated transition metal fragment. To isolate the plethora of borane, boryl, and borylene complexes, chemists have also used the coordination sphere of transition metals to stabilize reactive motifs in these molecules. In this Account, we summarize our results showing that increasingly synthetically challenging targets such as iminoboryl (B≡N), oxoboryl (B≡O), and diborene (B═B) fragments can be stabilized in the coordination sphere of late transition metals. This journey began with the isolation of two new iminoboryl ligands trans-[(Cy3P)2(Br)M(B≡N(SiMe3))] (M = Pd, Pt) attached to palladium and platinum fragments. The synthesis involved oxidative addition of the B-Br bond in (Me3Si)2N═BBr2 to [M(PCy3)2] (M = Pt, Pd) and the subsequent elimination of Me3SiBr at room temperature. Variation of the metal, the metal-bound coligands, and the substituent at the nitrogen atom afforded a series of analogous iminoboryl complexes. Following the same synthetic strategy, we also synthesized the first oxoboryl complex trans-[(Cy3P)2BrPt(BO)]. The labile bromide ligand adjacent to platinum makes the complex a viable candidate for further substitution reactions, which led to a number of new oxoboryl complexes. In addition to allowing us to isolate these fundamental compounds, the synthetic strategy is very convenient and minimizes byproducts. We also discuss the reaction chemistry of these types of compounds. In addition to facilitating the isolation of compounds with B≡E (E = N, O) triple bonds, the platinum fragment can also stabilize a

  3. Multiple superhyperfine fields in a {DyFe2Dy} coordination cluster revealed using bulk susceptibility and (57)Fe Mössbauer studies.

    PubMed

    Peng, Yan; Mereacre, Valeriu; Anson, Christopher E; Powell, Annie K

    2016-08-01

    A [DyFeDy(μ3-OH)2(pmide)2(p-Me-PhCO2)6] coordination cluster, where pmideH2 = N-(2-pyridylmethyl)iminodiethanol, has been synthesized and the magnetic properties studied. The dc magnetic measurements reveal dominant antiferromagnetic interactions between the metal centres. The ac measurements reveal zero-field quantum tunnelling of the magnetisation (QTM) which can be understood, but not adequately modelled, in terms of at least three relaxation processes when appropriate static (dc) fields are applied. To investigate this further, (57)Fe Mössbauer spectroscopy was used and well-resolved nuclear hyperfine structures could be observed, showing that on the Mössbauer time scale, without applied field or else with very small applied fields, the iron nuclei experience three or more superhyperfine fields arising from the slow magnetisation reversal of the strongly polarized fields of the Dy(III) ions. PMID:27424877

  4. Screening of free-living rhizospheric bacteria for their multiple plant growth promoting activities.

    PubMed

    Ahmad, Farah; Ahmad, Iqbal; Khan, M S

    2008-01-01

    Plant growth promoting rhizobacteria (PGPR) are known to influence plant growth by various direct or indirect mechanisms. In search of efficient PGPR strains with multiple activities, a total of 72 bacterial isolates belonging to Azotobacter, fluorescent Pseudomonas, Mesorhizobium and Bacillus were isolated from different rhizospheric soil and plant root nodules in the vicinity of Aligarh. These test isolates were biochemically characterized. These isolates were screened in vitro for their plant growth promoting traits like production of indoleacetic acid (IAA), ammonia (NH(3)), hydrogen cyanide (HCN), siderophore, phosphate solubilization and antifungal activity. More than 80% of the isolates of Azotobacter, fluorescent Pseudomonas and Mesorhizobium ciceri produced IAA, whereas only 20% of Bacillus isolates was IAA producer. Solubilization of phosphate was commonly detected in the isolates of Bacillus (80%) followed by Azotobacter (74.47%), Pseudomonas (55.56%) and Mesorhizobium (16.67%). All test isolates could produce ammonia but none of the isolates hydrolyzed chitin. Siderophore production and antifungal activity of these isolates except Mesorhizobium were exhibited by 10-12.77% isolates. HCN production was more common trait of Pseudomonas (88.89%) and Bacillus (50%). On the basis of multiple plant growth promoting activities, eleven bacterial isolates (seven Azotobacter, three Pseudomonas and one Bacillus) were evaluated for their quantitative IAA production, and broad-spectrum (active against three test fungi) antifungal activity. Almost at all concentration of tryptophan (50-500 microg/ml), IAA production was highest in the Pseudomonas followed by Azotobacter and Bacillus isolates. Azotobacter isolates (AZT(3), AZT(13), AZT(23)), Pseudomonas (Ps(5)) and Bacillus (B(1)) showed broad-spectrum antifungal activity on Muller-Hinton medium against Aspergillus, one or more species of Fusarium and Rhizoctonia bataticola. Further evaluation of the isolates

  5. Multiple expression of molecular information: enforced generation of different supramolecular inorganic architectures by processing of the same ligand information through specific coordination algorithms

    PubMed

    Funeriu; Lehn; Fromm; Fenske

    2000-06-16

    The multisubunit ligand 2 combines two complexation substructures known to undergo, with specific metal ions, distinct self-assembly processes to form a double-helical and a grid-type structure, respectively. The binding information contained in this molecular strand may be expected to generate, in a strictly predetermined and univocal fashion, two different, well-defined output inorganic architectures depending on the set of metal ions, that is, on the coordination algorithm used. Indeed, as predicted, the self-assembly of 2 with eight CuII and four CuI yields the intertwined structure D1. It results from a crossover of the two assembly subprograms and has been fully characterized by crystal structure determination. On the other hand, when the instructions of strand 2 are read out with a set of eight CuI and four MII (M = Fe, Co, Ni, Cu) ions, the architectures C1-C4, resulting from a linear combination of the two subprograms, are obtained, as indicated by the available physico-chemical and spectral data. Redox interconversion of D1 and C4 has been achieved. These results indicate that the same molecular information may yield different output structures depending on how it is processed, that is, depending on the interactional (coordination) algorithm used to read it. They have wide implications for the design and implementation of programmed chemical systems, pointing towards multiprocessing capacity, in a one code/ several outputs scheme, of potential significance for molecular computation processes and possibly even with respect to information processing in biology. PMID:10926214

  6. Transcriptional Activation of Human Matrix Metalloproteinase-9 Gene Expression by Multiple Coactivators

    PubMed Central

    Zhao, Xueyan; Benveniste, Etty N.

    2008-01-01

    Summary Matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme for matrix proteins, chemokines and cytokines, is a major target in cancer and autoimmune diseases since it is aberrantly upregulated. To control MMP-9 expression in pathological conditions, it is necessary to understand the regulatory mechanisms of MMP-9 expression. MMP-9 gene expression is regulated primarily at the transcriptional level. In this study, we investigated the role of multiple coactivators in regulating MMP-9 transcription. We demonstrate that multiple transcriptional coactivators are involved in MMP-9 promoter activation, including CBP/p300, PCAF, CARM1 and GRIP1. Furthermore, enhancement of MMP-9 promoter activity requires the histone acetyltransferase activity of PCAF but not that of CBP/p300, and the methyltransferase activity of CARM1. More importantly, these coactivators are not only able to activate MMP-9 promoter activity independently, but also function in a synergistic manner. Significant synergy was observed among CARM1, p300 and GRIP1, which is dependent on the interaction of p300 and CARM1 with the AD1 and AD2 domains of GRIP1, respectively. This suggests the formation of a ternary coactivator complex on the MMP-9 promoter. Chromatin immunoprecipitation assays demonstrate that these coactivators associate with the endogenous MMP-9 promoter, and that siRNA knockdown of expression of these coactivators reduces endogenous MMP-9 expression. Taken together, these studies demonstrate a new level of transcriptional regulation of MMP-9 expression by the cooperative action of coactivators. PMID:18790699

  7. Profiling of Multiple Targets of Artemisinin Activated by Hemin in Cancer Cell Proteome.

    PubMed

    Zhou, Yiqing; Li, Weichao; Xiao, Youli

    2016-04-15

    The antimalarial drug artemisinin is found to have diverse biological activities ranging from anti-inflammatory to anticancer properties; however, as of today, the cellular targets and mechanism of action of this important compound have remained elusive. Here, we report the global protein target profiling of artemisinin in the HeLa cancer cell proteome using a chemical proteomics approach. In the presence of hemin, multiple proteins were targeted by artemisinin probe through covalent modification. Further studies revealed that reducing of hemin to heme by protein thiols was essential for endoperoxide activation and subsequent protein alkylation. Artemisinin may exert its synergistic therapeutic anticancer effects via modulation of a variety of cellular pathways through acting on multiple targets. PMID:26854499

  8. 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

  9. Active microdisk resonators in an optical code division multiple access system

    NASA Astrophysics Data System (ADS)

    Akhavan, Hooman

    2013-02-01

    An optical code division multiple access design consisting of a set of active microdisks coupled to a waveguide bus for both encoder and decoder is presented. This integrated design is beneficial for secure transmission of data through an optical fiber channel. Device optimization and performance analysis shows dependence of the output signal quality on number of users and necessity of proper adjustment of quality factor of the resonators considering intended transmitted data rate.

  10. 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.

  11. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. PMID:27285815

  12. Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers.

    PubMed

    Stern, Josh Lewis; Theodorescu, Dan; Vogelstein, Bert; Papadopoulos, Nickolas; Cech, Thomas R

    2015-11-01

    Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression. PMID:26515115

  13. Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers

    PubMed Central

    Stern, Josh Lewis; Theodorescu, Dan; Vogelstein, Bert; Papadopoulos, Nickolas; Cech, Thomas R.

    2015-01-01

    Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression. PMID:26515115

  14. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    PubMed Central

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-01-01

    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. PMID:26147422

  15. Promoter activity 5′ of Dbeta2 is coordinated by E47, Runx1, and GATA-3

    PubMed Central

    McMillan, Ruth E.; Sikes, Michael L.

    2009-01-01

    V(D)J recombination involves the stepwise assembly of B and T cell receptor genes as lymphocytes progress through the early stages of development. While the mechanisms that restrict each step in recombination to its appropriate developmental stage are largely unknown, they share many of the components that regulate transcription. For example, enhancer-dependent modifications in histone acetylation and methylation are essential for both germline transcription and rearrangement of antigen receptor genes. Promoters positioned proximal to individual D and J gene segments in Tcra, Tcrb, Tcrd, IgH, and Igk also contribute to antigen receptor gene assembly, though their effects appear more localized than those of enhancers. Tcrb assembly initiates with D-to-J joining at each of two D-J-C gene segment clusters in DN1/2 thymocytes. DJ joints are fused with Vβ elements to complete Tcrb recombination in DN3 cells. We have previously shown that Dβ2 is flanked by upstream and downstream promoters, with the 5′ promoter being held inactive until D-to-J recombination deletes the NFκB-dependent 3′ promoter. We now report that activity of the 5′ promoter reflects a complex interplay between Runx1, GATA-3, and E47 transcription factors. In particular, while multiple E47 and Runx1 binding sites clustered near the Dβ2 5′RS and overlapping inr elements define the core 5′PDβ2, they act in concert with an array of upstream GATA-3 sites to overcome the inhibitory effects of a 110 bp distal polypurine·polypyrimidine (R·Y) tract. The dependence of 5′PDβ2 on E47 is consistent with the reported role of E proteins in post-DN1 thymocyte development and V-to-DJβ recombination. PMID:19592096

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial

    PubMed Central

    Eddleston, Michael; Juszczak, Edmund; Buckley, Nick A; Senarathna, Lalith; Mohamed, Fahim; Dissanayake, Wasantha; Hittarage, Ariyasena; Azher, Shifa; Jeganathan, K; Jayamanne, Shaluka; Sheriff, MH Rezvi; Warrell, David A

    2008-01-01

    Summary Background The case-fatality for intentional self-poisoning in the rural developing world is 10–50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. Methods We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. Findings Mortality did not differ between the groups. 97 (6·3%) of 1531 participants in the multiple-dose group died, compared with 105 (6·8%) of 1554 in the no charcoal group (adjusted odds ratio 0·96, 95% CI 0·70–1·33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. Interpretation We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed. PMID:18280328

  2. Multiple EMG activity and intracortical inhibition and facilitation during a fine finger movement under pressure.

    PubMed

    Tanaka, Yoshifumi; Funase, Kozo; Sekiya, Hiroshi; Sasaki, Joyo; Takemoto, Toru

    2011-01-01

    The 1st purpose of this study was to examine multiple electromyography (EMG) during voluntary hand movements. A secondary purpose was to investigate possible effects of pressure on intracortical inhibition (ICI) and intracortical facilitation (ICF) functions of the motor cortex, using paired-pulse transcranial magnetic stimulation. Twelve participants traced a 15-cm diameter target circle using a small laser pointer attached to the right index finger. After 5 acquisition trials, they performed 3 nonpressure trials followed by 3 pressure trials. The results showed that pressure had effects not only on agonist EMG activity but also on multiple muscles, such as synergist. In addition, a decrease in ICI and an increase in ICF were both observed under pressure for muscles other than the agonist. PMID:21218324

  3. 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.

  4. 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

  5. Simultaneous Segmentation of Prostatic Zones Using Active Appearance Models With Multiple Coupled Levelsets

    PubMed Central

    Toth, Robert; Ribault, Justin; Gentile, John; Sperling, Dan; Madabhushi, Anant

    2013-01-01

    In this work we present an improvement to the popular Active Appearance Model (AAM) algorithm, that we call the Multiple-Levelset AAM (MLA). The MLA can simultaneously segment multiple objects, and makes use of multiple levelsets, rather than anatomical landmarks, to define the shapes. AAMs traditionally define the shape of each object using a set of anatomical landmarks. However, landmarks can be difficult to identify, and AAMs traditionally only allow for segmentation of a single object of interest. The MLA, which is a landmark independent AAM, allows for levelsets of multiple objects to be determined and allows for them to be coupled with image intensities. This gives the MLA the flexibility to simulataneously segmentation multiple objects of interest in a new image. In this work we apply the MLA to segment the prostate capsule, the prostate peripheral zone (PZ), and the prostate central gland (CG), from a set of 40 endorectal, T2-weighted MRI images. The MLA system we employ in this work leverages a hierarchical segmentation framework, so constructed as to exploit domain specific attributes, by utilizing a given prostate segmentation to help drive the segmentations of the CG and PZ, which are embedded within the prostate. Our coupled MLA scheme yielded mean Dice accuracy values of .81, .79 and .68 for the prostate, CG, and PZ, respectively using a leave-one-out cross validation scheme over 40 patient studies. When only considering the midgland of the prostate, the mean DSC values were .89, .84, and .76 for the prostate, CG, and PZ respectively. PMID:23997571

  6. Simultaneous Segmentation of Prostatic Zones Using Active Appearance Models With Multiple Coupled Levelsets.

    PubMed

    Toth, Robert; Ribault, Justin; Gentile, John; Sperling, Dan; Madabhushi, Anant

    2013-09-01

    In this work we present an improvement to the popular Active Appearance Model (AAM) algorithm, that we call the Multiple-Levelset AAM (MLA). The MLA can simultaneously segment multiple objects, and makes use of multiple levelsets, rather than anatomical landmarks, to define the shapes. AAMs traditionally define the shape of each object using a set of anatomical landmarks. However, landmarks can be difficult to identify, and AAMs traditionally only allow for segmentation of a single object of interest. The MLA, which is a landmark independent AAM, allows for levelsets of multiple objects to be determined and allows for them to be coupled with image intensities. This gives the MLA the flexibility to simulataneously segmentation multiple objects of interest in a new image. In this work we apply the MLA to segment the prostate capsule, the prostate peripheral zone (PZ), and the prostate central gland (CG), from a set of 40 endorectal, T2-weighted MRI images. The MLA system we employ in this work leverages a hierarchical segmentation framework, so constructed as to exploit domain specific attributes, by utilizing a given prostate segmentation to help drive the segmentations of the CG and PZ, which are embedded within the prostate. Our coupled MLA scheme yielded mean Dice accuracy values of .81, .79 and .68 for the prostate, CG, and PZ, respectively using a leave-one-out cross validation scheme over 40 patient studies. When only considering the midgland of the prostate, the mean DSC values were .89, .84, and .76 for the prostate, CG, and PZ respectively. PMID:23997571

  7. Early Stages of Zebrafish Eye Formation Require the Coordinated Activity of Wnt11, Fz5, and the Wnt/β-Catenin Pathway

    PubMed Central

    Cavodeassi, Florencia; Carreira-Barbosa, Filipa; Young, Rodrigo M.; Concha, Miguel L.; Allende, Miguel L.; Houart, Corinne; Tada, Masazumi; Wilson, Stephen W.

    2009-01-01

    Summary During regional patterning of the anterior neural plate, a medially positioned domain of cells is specified to adopt retinal identity. These eye field cells remain coherent as they undergo morphogenetic events distinct from other prospective forebrain domains. We show that two branches of the Wnt signaling pathway coordinate cell fate determination with cell behavior during eye field formation. Wnt/β-catenin signaling antagonizes eye specification through the activity of Wnt8b and Fz8a. In contrast, Wnt11 and Fz5 promote eye field development, at least in part, through local antagonism of Wnt/β-catenin signaling. Additionally, Wnt11 regulates the behavior of eye field cells, promoting their cohesion. Together, these results allow us to postulate a model in which Wnt11 and Fz5 signaling promotes early eye development through the coordinated antagonism of signals that suppress retinal identity and promotion of coherence of eye field cells. PMID:15996547

  8. Sensorimotor Encoding by Synchronous Neural Ensemble Activity at Multiple Levels of the Somatosensory System

    NASA Astrophysics Data System (ADS)

    Nocolelis, Miguel A. L.; Baccala, Luiz A.; Lin, Rick C. S.; Chapin, John K.

    1995-06-01

    Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

  9. REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells.

    PubMed

    Immaneni, A; Lawinger, P; Zhao, Z; Lu, W; Rastelli, L; Morris, J H; Majumder, S

    2000-09-01

    The RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress transcription of a battery of neuronal differentiation genes in non-neuronal cells by binding to a specific consensus DNA sequence present in their regulatory regions. However, REST/NRSF(-/-) mice suggest that the absence of REST/NRSF-dependent repression alone is not sufficient for the expression of these neuronal differentiation genes and that the presence of other promoter/enhancer-specific activators is required. Here we describe the construction of a recombinant transcription factor, REST-VP16, by replacing repressor domains of REST/NRSF with the activation domain of a viral activator VP16. In transient transfection experiments, REST-VP16 was found to operate through RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE), activate plasmid-encoded neuronal promoters in various mammalian cell types and activate cellular REST/NRSF target genes, even in the absence of factors that are otherwise required to activate such genes. Efficient expression of REST-VP16 through adenoviral vectors in NT2 cells, which resemble human committed neuronal progenitor cells, was found to cause activation of multiple neuronal genes that are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be used as a unique tool to study neuronal differentiation pathways and neuronal diseases that arise due to the deregulation of this process. PMID:10954611

  10. 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

  11. Reliability of Accelerometer Scores for Measuring Sedentary and Physical Activity Behaviors in Persons With Multiple Sclerosis.

    PubMed

    Klaren, Rachel E; Hubbard, Elizabeth A; Zhu, Weimo; Motl, Robert W

    2016-04-01

    This brief research note examined the reliability of scores from an accelerometer as measures of sedentary and physical activity behaviors in persons with multiple sclerosis (MS). The analysis was performed on a combined data set from 2 previous longitudinal investigations of physical activity in MS. We focused on the number of days required to reliably estimate sedentary behavior, based on time spent in sedentary behavior per day and number of sedentary breaks, number of long sedentary bouts, and average length of sedentary bouts per day. We further examined the number of days required to reliably estimate physical activity behavior, based on time spent in light and moderate-to-vigorous physical activity and average length of activity bouts per day. Between 4-6 days of monitoring and 3-7 days of monitoring were necessary for good reliability of scores from all sedentary outcomes and physical activity outcomes, respectively. These results should guide research and practice examining sedentary and physical activity behaviors using accelerometry in persons with MS. PMID:27078272

  12. 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

  13. Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing- Remitting Multiple Sclerosis

    PubMed Central

    Mancuso, Roberta; Hernis, Ambra; Agostini, Simone; Rovaris, Marco; Caputo, Domenico; Fuchs, Dietmar; Clerici, Mario

    2015-01-01

    Background Interferon gamma (IFN-γ) production induces the transcription of indoleamine 2,3 dioxygenase (IDO) resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS) patients. Methods IDO and interferon-γ (IFN-γ) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration – a protein released by macrophages upon IFN-γ stimulation – were measured in 51 individuals: 36 relapsing remitting (RR)-MS patients (21 in acute phase -AMS, 15 in stable phase -SMS) and 15 healthy controls (HC). PBMCs samples in AMS patients were collected before (BT-AMS) and during glucocorticoids-based therapy (DT-AMS). Results IDO expression was increased and IFN-γ was decreased (p<0.001) in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001). Serum neopterin concentration followed the same trend as IDO expression and activity. Conclusions Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS. PMID:26110930

  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. 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.

  16. Environmental correlates of physical activity in multiple sclerosis: A cross-sectional study

    PubMed Central

    Doerksen, Shawna E; Motl, Robert W; McAuley, Edward

    2007-01-01

    Background Multiple sclerosis (MS) is a chronic neurological disease that is associated with physical inactivity. Understanding the factors that correlate with physical activity is important for developing effective physical activity promotion programs for this population. Thus, we conducted a cross-sectional study that examined the association between features of the built environment with self-reported and objectively measured physical activity behaviour in adults with MS. Methods Participants with MS (n = 196) were sent a questionnaire packet that included self-report measures of the built environment and physical activity and a pedometer in the mail and were instructed to complete the questionnaires and wear the device for seven days. Participants returned the completed questionnaires in a pre-stamped, pre-addressed envelope. Bivariate correlation analysis was conducted for examining associations between items on the environmental questionnaire with the two measures of physical activity. Stepwise regression analysis was conducted for determining the independent contributions of the significant environmental correlates for explaining variation in physical activity. Results Correlational analysis indicated that presence of shops, stores, markets or other places within walking distance (r = .20; ρ = .18), presence of a transit stop within walking distance (r = .20; ρ = .16), and accessibility of free or low-cost recreation facilities (r = .16; ρ = .15) were related to pedometer, but not self-reported, measured physical activity. Regression analysis indicated that the presence of a transit stop within walking distance independently explained 4% of variance in pedometer measured physical activity. Conclusion Physical activity is an important behaviour to promote among individuals with MS. This study indicated that aspects of the built environment are related to this health promoting behaviour among those with MS. Further research should focus on the longitudinal

  17. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells.

    PubMed

    Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Okawa, Yutaka; Raje, Noopur; Podar, Klaus; Mitsiades, Constantine; Munshi, Nikhil C; Richardson, Paul G; Carrasco, Ruben D; Anderson, Kenneth C

    2009-07-30

    Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappaB activity by blocking proteasomal degradation of inhibitor of kappaBalpha (IkappaBalpha). Bortezomib inhibits inducible NF-kappaB activity; however, its impact on constitutive NF-kappaB activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated IkappaBalpha expression and triggered NF-kappaB activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 (RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-kappaB activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced IkappaBalpha down-regulation associated with NF-kappaB activation. Molecular mechanisms whereby bortezomib induced IkappaBalpha down-regulation were further examined. Bortezomib triggered phosphorylation of IkappaB kinase (IKKbeta) and its upstream receptor-interacting protein 2, whereas IKKbeta inhibitor MLN120B blocked bortezomib-induced IkappaBalpha down-regulation and NF-kappaB activation, indicating receptor-interacting protein 2/IKKbeta signaling plays crucial role in bortezomib-induced NF-kappaB activation. Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells. PMID:19436050

  18. 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.

  19. 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

  20. 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

  1. An unequivocal example of cysteine proteinase activity affected by multiple electrostatic interactions.

    PubMed

    Taylor, M A; Baker, K C; Connerton, I F; Cummings, N J; Harris, G W; Henderson, I M; Jones, S T; Pickersgill, R W; Sumner, I G; Warwicker, J

    1994-10-01

    The role of electrostatic interactions between the ionizable Asp158 and the active site thiolate-imidazolium ion pair of some cysteine proteinases has been the subject of controversy for some time. This study reports the expression of wild type procaricain and Asp158Glu, Asp158Asn and Asp158Ala mutants from Escherichia coli. Purification of autocatalytically matured enzymes yielded sufficient fully active material for pH (kcat/Km) profiles to be obtained. Use of both uncharged and charged substrates allowed the effects of different reactive enzyme species to be separated from the complications of electrostatic effects between enzyme and substrate. At least three ionizations are detectable in the acid limb of wild type caricain and the Glu and Asn mutants. Only two pKa values, however, are detectable in the acid limb using the Ala mutant. Comparison of pH activity profiles shows that whilst an ionizable residue at position 158 is not essential for the formation of the thiolate-imidazolium ion pair, it does form a substantial part of the electrostatic field responsible for increased catalytic competence. Changing the position of this ionizable group in any way reduces activity. Complete removal of the charged group reduces catalytic competence even further. This work indicates that hydronations distant to the active site are contributing to the electrostatic effects leading to multiple active ionization states of the enzyme. PMID:7855143

  2. 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

  3. 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

  4. 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

  5. [In vitro activity of tigecycline against multiple resistant Acinetobacter baumannii and carbapenem resistant Klebsiella pneumoniae isolates].

    PubMed

    Arikan Akan, Ozay; Uysal, Sevil

    2008-04-01

    In order to detect the in vitro activity of tigecycline against multiple resistant gram-negative bacilli isolated in our hospital, tigecycline susceptibilities of clinical isolates of multiple and/or panresistant 100 Acinetobacter baumannii isolates, and 38 carbapenem resistant Klebsiella pneumoniae (17 of which were panresistant), obtained between January 2005 and August 2007, were evaluated by using E-test (AB Biodisc, Sweden). Carbapenem resistance rate was found to be 59% for A.baumannii, using Vitek2 Compact System (Bio-Merieux, France) which is present in our laboratory for routine use. Minimal inhibitory concentration (MIC) levels for tigecycline were < or =2 mcg/ml in 93% of the isolates while the MIC level was 3 mcg/ml for 7% of the isolates. Tigecycline MIC50 and MIC 90 values were 1.5 and 2 mcg/ml, respectively. Among K. pneumoniae the least resistance was detected against amikacin (52.6% resistant) while tigecycline MIC levels were between 0.13 mcg/ml and 2 mcg/ml. All of the K.pneumoniae strains were susceptible to tigecycline, and the MIC50 ve MIC90 values of these isolates were 1 mcg/ml and 1.5 mcg/ml, respectively. The in vitro susceptibility rates of tigecycline against multiple and/or panresistant A. baumannii and K. pneumoniae isolates are found to be promising for use in therapy. PMID:18697418

  6. 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.

  7. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    PubMed

    Wang, Yao; Zhao, Gao-Xiang; Xu, Li-Hui; Liu, Kun-Peng; Pan, Hao; He, Jian; Cai, Ji-Ye; Ouyang, Dong-Yun; He, Xian-Hui

    2014-01-01

    Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1) and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+) T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65), it blocked the nuclear translocation of NF-κB (p65). In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response. PMID:24587010

  8. Cucurbitacin IIb Exhibits Anti-Inflammatory Activity through Modulating Multiple Cellular Behaviors of Mouse Lymphocytes

    PubMed Central

    Liu, Kun-Peng; Pan, Hao; He, Jian; Cai, Ji-Ye; Ouyang, Dong-Yun; He, Xian-Hui

    2014-01-01

    Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65), it blocked the nuclear translocation of NF-κB (p65). In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response. PMID:24587010

  9. BLADE-ON-PETIOLE1 Coordinates Organ Determinacy and Axial Polarity in Arabidopsis by Directly Activating ASYMMETRIC LEAVES2[C][W

    PubMed Central

    Jun, Ji Hyung; Ha, Chan Man; Fletcher, Jennifer C.

    2010-01-01

    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 BLADE-ON-PETIOLE1 (BOP1) and BOP2 function as transcriptional activators during Arabidopsis thaliana leaf formation. We identify as a direct target of BOP1 induction the ASYMMETRIC LEAVES2 (AS2) gene, which promotes leaf cell fate specification and adaxial polarity. We find that BOP1 associates with the AS2 promoter and that BOP1 and BOP2 are required for AS2 activation specifically in the proximal, adaxial region of the leaf, demonstrating a role for the BOP proteins as proximal-distal as well as adaxial-abaxial patterning determinants. Furthermore, repression of BOP1 and BOP2 expression by the indeterminacy-promoting KNOX gene SHOOTMERISTEMLESS is critical to establish a functional embryonic shoot apical meristem. Our data indicate that direct activation of AS2 transcription by BOP1 and BOP2 is vital for generating the conditions for KNOX repression at the leaf base and may represent a conserved mechanism for coordinating leaf morphogenesis with patterning along the adaxial-abaxial and the proximal-distal axes. PMID:20118228

  10. 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.

  11. Long-term assessment of No Evidence of Disease Activity with natalizumab in relapsing multiple sclerosis.

    PubMed

    Prosperini, Luca; Fanelli, Fulvia; Pozzilli, Carlo

    2016-05-15

    In this study we assessed the proportion of patients with relapsing multiple sclerosis (R-MS) who had No Evidence of Disease Activity (NEDA-3), defined as absence of relapses, absence of confirmed disability worsening, and absence of radiological activity (detected by magnetic resonance imaging of the brain and spinal cord) up to 7years after starting natalizumab. Out of 152 patients considered, 58 were still on treatment and 94 discontinued treatment after a median time of 3years. According to an intention-to-treat approach, 52 (34%) patients maintained the NEDA status at the end of follow-up. The proportion of patients with NEDA increases to 41% after excluding from the analysis 64 patients who discontinued natalizumab due to concerns about progressive multifocal leukoencephalopathy. Our findings suggest that natalizumab may ensure higher proportion of patients achieving sustained long-term disease remission than that previously reported with self-injectable treatments (<10%). PMID:27084235

  12. 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. PMID:27309150

  13. Reactions of [Cu(X)(BPEP-Ph)] (X = PF6, SbF6) with silyl compounds. Cooperative bond activation involving non-coordinating anions.

    PubMed

    Nakajima, Yumiko; Tsuchimoto, Takahiro; Chang, Yung-Hung; Takeuchi, Katsuhiko; Ozawa, Fumiyuki

    2016-02-01

    Bond activation of silyl compounds, assisted by the cooperative action of non-coordinating anions, is achieved using Cu(I) complexes coordinated with a PNP-pincer type phosphaalkene ligand, [Cu(X)(BPEP-Ph)] (X = PF6 (1a), SbF6 (1b); BPEP-Ph = 2,6-bis[1-phenyl-2-(2,4,6-tri-tert-butylphenyl)-2-phosphaethenyl]pyridine). Complexes 1a and 1b react with Me3SiCN to form Me3SiF and Cu(i) cyanide complexes of the formula [Cu(CN-EF5)(BPEP-Ph)] (E = P (2a), Sb (2b)), in which the CN ligand is associated with the EF5 group arising from EF6(-). Formation of the intermediary isonitrile complex [Cu(CNSiMe3)(BPEP-Ph)](+)SbF6(-) (3b) is confirmed by its isolation. Thus, a two-step reaction process involving coordination of Me3SiCN, followed by nucleophilic attack of SbF6(-) on the silicon atom of 3b is established for the conversion of 1b to 2b. Complex 1b cleaves the H-Si bond of PhMe2SiH as well. The isolation and structural identification of [Cu(BPEP-Ph)](+)BAr(F)4(-) (1c) (BAr(F)4 = B{3,5-(CF3)2C6H3}4) as a rare example of a T-shaped, three-coordinated Cu(i) complex is reported. PMID:26455594

  14. Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells.

    PubMed

    Donnenberg, Vera S; Meyer, E Michael; Donnenberg, Albert D

    2009-01-01

    Multiple drug resistance, mediated by the expression and activity of ABC-transporters, is a major obstacle to antineoplastic therapy. Normal tissue stem cells and their malignant counterparts share MDR transporter activity as a major mechanism of self-protection. Although MDR activity is upregulated in response to substrate chemotherapeutic agents, it is also constitutively expressed on both normal tissue stem cells and a subset of tumor cells prior to the initiation of therapy, representing a built-in obstacle to therapeutic ratio. Constitutive and induced MDR activity can be detected in cellular subsets of disaggregated tissues, using the fluorescent substrates Rhodamine 123 and Hoechst 33342 for ABCB1 (also known as P-gp and MDR1) and ABCG2 (BCRP1). In this chapter, we will describe the complete procedure for the detection of MDR activity, including: (1) Preparing single-cell suspensions from tumor and normal tissue specimens; (2) An efficient method to perform cell surface marker staining on large numbers of cells; (3) Flow cytometer setup and controls; (4) Simultaneous measurement of Hoechst 33342 and Rhodamine123 transport; and (5) Data acquisition and analysis. PMID:19582433

  15. 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

  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. The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation.

    PubMed

    Helfer, Christine M; Yan, Junpeng; You, Jianxin

    2014-08-01

    The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb), a functional interaction partner of Brd4 in transcription activation, is important for E2's transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP) analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2's interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+), a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV) life cycle. PMID:25140737

  18. Persistent activation of microglia and NADPH drive hippocampal dysfunction in experimental multiple sclerosis

    PubMed Central

    Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

    2016-01-01

    Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID:26887636

  19. E.E.G. and multiple unit activity during ketamine and barbiturate anaesthesia.

    PubMed

    Tamásy, V; Korányi, L; Tekeres, M

    1975-12-01

    Cortical e.e.g. and multiple unit activity (m.u.a.) of the mesencephalic reticular formation, the anterior hypothalamic area, the basal nuclear group of the amygdala and the dorsal hippocampus were studied before and following i.p. injection of different doses of ketamine hydrochloride and a barbiturate in cats with chronically implanted electrodes. Barbiturate administration resulted in a rapid decrease in m.u.a. in the mesencephalic reticular formation which was accompanied by a significant decrease of activity in the limbic structures. No m.u.a. response was observed to visual, acoutic or somatosensory stimulation or to pain. The m.u.a. of the mesencephalic reticular formation and limbic structures increased gradually following ketamine injection. Intermittent or continuous hypersynchronous activity was characteristic in the cortical e.e.g. During the hypersynchronous activity the responsiveness of m.u.a. in the mesencephalic reticular formation, to visual and acoustic stimuli, was blocked. Somatosensory and painful stimulation, however, resulted in a significant increase in the activity both of the mesencephalic reticular formation and of the limbic neuronal pools. PMID:1218162

  20. Sequential activation of multiple grounding pads reduces skin heating during radiofrequency tumor ablation

    PubMed Central

    HAEMMERICH, DIETER; SCHUTT, DAVID JAMES

    2009-01-01

    Purpose Radiofrequency (RF) tumor ablation has become an accepted treatment modality for tumors not amenable to surgery. Skin burns due to ground pad heating may become a limiting factor for further increase in ablation zone dimensions and generator power. We investigated a method were groups of ground pads are sequentially activated to reduce skin heating. Methods We compared conventional operation (i.e. simultaneous connection of all pads) to sequentially switched activation of the pads where different pad combinations are active for periods of ∼0.3 − 8 s. The timing during sequential activation was adjusted to keep the leading edge temperature equal between the pads. We created Finite Element Method computer models of three pads (5 × 5 cm, 1 cm apart) placed in line with the RF electrode on a human thigh to determine differences in tissue heating during simultaneous and sequential ground pad activation. We performed experiments with three ground pads (5 × 10 cm, 4 cm apart) placed on a tissue phantom (1.5 A, 12 min) and measured pad surface and leading edge temperatures. Results Temperature rise below the leading edge for proximal, middle and distal ground pad in relation to active electrode location was 5.9°C ± 0.1°C, 0.8°C ± 0.1°C and 0.3°C ± 0.1°C for conventional operation, and 3.3°C ± 0.1°C, 3.4°C ± 0.2°C and 3.4°C ± 0.2°C for sequentially activated operation in the experiments (p < 0.001). Conclusion Sequential activation of multiple ground pads resulted in reduced maximum tissue temperature. This may reduce the incidence of ground pad burns and may allow higher power RF generators. PMID:18038286

  1. 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

  2. Home-based system for physical activity monitoring in patients with multiple sclerosis (Pilot study)

    PubMed Central

    2014-01-01

    Background Limitations in physical activity are considered as a key problem in patients with multiple sclerosis (PwMS). Contemporary methods to assess the level of physical activity in PwMS are regular clinical observation. However, these methods either rely on high recall and accurate reporting from the patients (e.g. self-report questionnaires), or they are conducted during a particular clinical assessment with predefined activities. Therefore, the main aim of this pilot study was to develop an objective method to gather information about the real type and intensity of daily activities performed by PwMS in every-day living situations using an accelerometer. Furthermore, the accelerometer-derived measures are investigated regarding their potential for discriminating between different MS groups. Methods Eleven PwMS that were able to walk independently (EDSS ≤ 5) were divided into two groups: mild disability (EDSS 1–2.5; n = 6) and moderate disability (EDSS 3 –5; n = 5). Participants made use of an activity monitor device attached to their waist during their normal daily activities over 4 measurements. Activity parameters were assessed and compared for the time of each participant’s first measurement and follow-up measurement. Furthermore, differences between both subgroups, and the correlation of activity parameters with the clinical neurological variable (EDSS) were investigated. Results Participants showed significant decline in step count (p = 0.008), maximum walking speed (p = 0.02) and physical activity intensity (p = 0.03) throughout the study period. Compared to the mild subgroup, moderate affected participant accumulated less number of steps (G1: 9214.33 ± 2439.11, G2: 5018.13 ± 2416.96; p < 0.005) and were slower (G1: 1.48 ± 0.19, G2: 1.12 ± 0.44; p = 0.03). Additionally, the EDSS correlated negatively with mean walking speed (r = - 0.71, p = 0.01) and steps count (r = - 0.54, p

  3. Gender differential effects of developmental exposure to methyl-mercury, polychlorinated biphenyls 126 or 153, or its combinations on motor activity and coordination.

    PubMed

    Cauli, Omar; Piedrafita, Blanca; Llansola, Marta; Felipo, Vicente

    2013-09-01

    Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are persistent organic pollutants accumulating in the food chain. Pre- and neonatal exposure to these neurotoxicants may affect brain development and lead to long-lasting alterations in cerebral function, which can result in motor alterations in youth and/or adulthood. Some neurotoxicants induce gender specific effects. The aims of the present work were to: (1) assess the effects of developmental exposure to MeHg, PCB 153 or PCB 126 on spontaneous locomotor and vertical activity and motor coordination when the rats are 2-month old; (2) assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 alter the effects of the individual neurotoxicants; (3) follow the progression of motor alterations when the rats are 3-, 5- and 7-month old; (4) assess if the effects are similar or different in males and females. Pregnant rats were treated with MeHg (0.5mg/kgday); PCB126 (100ng/kgday) or PCB153 (1mg/kgday) or with combinations of MeHg with each PCB, administered in food from gestational day 7 until weaning at post-natal day 21. PCB 126 impaired motor coordination at 2 months in males but not in females. PCB 153 impaired coordination both in males and females. Combinations of MeHg with PCB153 or PCB126 did not affect motor coordination, indicating that MeHg counteracts the effects of the PBCs. The combination of MeHg and PCB153 induces hypolocomotion at 2 months but hyperactivity at 7 months while the individual compounds did not induce any effect. PCB126 induced gender selective effects, reducing locomotor activity at 2 months in females but not in males. The combination of MeHg and PCB126 behaves as PCB126 alone. All compounds and combinations tested induce gender-selective alterations in vertical activity. The effects on locomotor and vertical activity change with age in the same rats. At 2 months all compounds and combinations reduce vertical activity in females but not in males. At 7 months

  4. 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

  5. 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). PMID:27207680

  6. Drought-Induced Effects on Nitrate Reductase Activity and mRNA and on the Coordination of Nitrogen and Carbon Metabolism in Maize Leaves1

    PubMed Central

    Foyer, Christine H.; Valadier, Marie-Hélène; Migge, Andrea; Becker, Thomas W.

    1998-01-01

    Maize (Zea mays L.) plants were grown to the nine-leaf stage. Despite a saturating N supply, the youngest mature leaves (seventh position on the stem) contained little NO3− reserve. Droughted plants (deprived of nutrient solution) showed changes in foliar enzyme activities, mRNA accumulation, photosynthesis, and carbohydrate and amino acid contents. Total leaf water potential and CO2 assimilation rates, measured 3 h into the photoperiod, decreased 3 d after the onset of drought. Starch, glucose, fructose, and amino acids, but not sucrose (Suc), accumulated in the leaves of droughted plants. Maximal extractable phosphoenolpyruvate carboxylase activities increased slightly during water deficit, whereas the sensitivity of this enzyme to the inhibitor malate decreased. Maximal extractable Suc phosphate synthase activities decreased as a result of water stress, and there was an increase in the sensitivity to the inhibitor orthophosphate. A correlation between maximal extractable foliar nitrate reductase (NR) activity and the rate of CO2 assimilation was observed. The NR activation state and maximal extractable NR activity declined rapidly in response to drought. Photosynthesis and NR activity recovered rapidly when nutrient solution was restored at this point. The decrease in maximal extractable NR activity was accompanied by a decrease in NR transcripts, whereas Suc phosphate synthase and phosphoenolpyruvate carboxylase mRNAs were much less affected. The coordination of N and C metabolism is retained during drought conditions via modulation of the activities of Suc phosphate synthase and NR commensurate with the prevailing rate of photosynthesis. PMID:9576798

  7. Coordination Assembly of Discoid Nanoparticles.

    PubMed

    Hirai, Kenji; Yeom, Bongjun; Chang, Shu-Hao; Chi, Hang; Mansfield, John F; Lee, Byeongdu; Lee, Sungsik; Uher, Ctirad; Kotov, Nicholas A

    2015-07-27

    Supramolecular chemistry utilizes coordination bonds to assemble molecular building blocks into a variety of sophisticated constructs. However, traditional coordination assemblies are based on organic compounds that have limited ability to transport charge. Herein, we describe coordination assembly of anisotropic FeS2 pyrite nanoparticles (NPs) that can facilitate charge transport. Zn(2+) ions form supramolecular complexes with carboxylate end-groups on NP surface, leading to multiparticle sheets with liquid-crystal-like organization. Conductivity and Hall carrier mobility of the p-type layered semiconductor films with Zn(2+) coordination bridging exceed those known for coordination compounds, some by several orders of magnitude. The nanoscale porosity of the assembled sheets combined with fast hole transport leads to high electrocatalytic activity of the NP films. The coordination assembly of NPs embraces the versatility of several types of building blocks and opens a new design space for self-organized materials combining nanoscale and supramolecular structural motifs. PMID:26095101

  8. Croissance et developpment de l'enfant: 25 ans d'activities internationales coordonnees. Growth and Development of the Child: 25 Years of Internationally Coordinated Activities.

    ERIC Educational Resources Information Center

    Courrier, 1980

    1980-01-01

    This special issue of the "Courrier," a journal for professionals concerned with issues related to the physical and psychological development of children, provides (1) an overview of 25 years of internationally coordinated research, (2) a selection of papers published by the research teams, and (3) a description of the teams and their present…

  9. Pinatubo Emulation in Multiple Models (POEMs): planned co-ordinated experiments for the SPARC Stratospheric Sulphur and it's Role in Climate initiative (SSiRC)

    NASA Astrophysics Data System (ADS)

    Mann, Graham; Lee, Lindsay A.; Carslaw, Ken S.; Toohey, Matthew; Aquila, Valentina; Timmreck, Claudia; English, Jason M.; Neely, Ryan R., III

    2014-05-01

    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. A powerful new technique to quantify and attribute sources of uncertainty in complex global models is described by Lee et al. (2011). This involves "conditioning" a Gaussian emulator to replicate (gridbox by gridbox) the results from an ensemble of runs with the full complex 3D model. Once trained on the ensemble, a Monte Carlo simulation with the fast emulator can be carried out for a full variance-based sensitivity analysis. For example, Carslaw et al., (2013, Nature) used the approach to quantify the uncertainty in indirect aerosol forcing from a 3D global chemistry-aerosol-microphysics model, decomposing the variance attributed to 28 uncertain emissions-types/processes-parameters/model-structures. One component of SSiRC involves an intercomparison of a new generation of Earth System Models that simulate the stratospheric aerosol layer interactively. Following the kick-off meeting for SSiRC in October 2013, one component of the SSiRC activity will be for each model to run "perturbed physics ensembles" (PPEs) of the Pinatubo eruption across several uncertain parameters. The Gaussian emulation approach will the be carried out on each model to characterise and intercompare the magnitude and uncertainty of simulated climate effects. In this poster presentation we will present the overall plan for this "POEMS" analysis including the outcome of an expert elicitation to finalise which uncertain parameters are to be varied and their uncertainty ranges.

  10. In silico Investigation of the PglB Active Site Reveals Transient Catalytic States and Octahedral Metal Ion Coordination.

    PubMed

    Pedebos, Conrado; Arantes, Pablo Ricardo; Giesel, Guilherme Menegon; Verli, Hugo

    2015-11-01

    The last step of the bacterial N-glycosylation pathway involves PglB, an oligosaccharyltransferase, which is responsible for the en bloc transfer of a fully assembled oligosaccharide chain to a protein possessing the extended motif D/E-X-N-X-S/T. Recently, this molecule had its full structure elucidated, enabling the description of its domains and the proposition of a catalytic mechanism. By employing molecular dynamics simulations, we were able to evaluate structural aspects of PglB, suggesting prevalent motions that may bring insights into the mechanism of the glycosylated peptide detachment. Additionally, we identified transient states at the catalytic site, in which the previously described carboxamide twisting mechanism was observed. Aided by quantum mechanics calculations for each different conformational states of the catalytic site, we determined the presence of an octahedral metal coordination, along with the presence of one water molecule at the catalytic site. PMID:26220543

  11. FMRFamide-like immunoreactivity and arylamidase activity in turbellarians and nemerteans--evidence for a novel neurovascular coordinating system in nemerteans.

    PubMed

    Jennings, J B; Davenport, T R; Varndell, I M

    1987-01-01

    The tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) has been immunolocalized in the nervous systems of seven species of Turbellaria and four species of Nemertea. The 11 species represent all the major turbellarian and nemertean taxa, and illustrate most of the various life styles found in these animals. The FMRFamide-like reactivity coincides with histochemically demonstrable arylamidase activity in the nervous systems. It is suggested that the FMRFamide-like reactivity demonstrates the presence in these lower invertebrates of one or more biologically active peptides, analogous to those of higher invertebrates and chordates and acting as putative neurotransmitters and coordinators of growth, maturation and muscular activities. The arylamidases occurring with the peptides are probably an integral part of these peptide-mediated control systems. The nemertean vascular system is especially rich in arylamidases and is believed to be concerned primarily with peptidergic control of bodily functions, rather than with transport of metabolites. PMID:2882945

  12. Probing the coordinative unsaturation and local environment of Ti³⁺ sites in an activated high-yield Ziegler-Natta catalyst.

    PubMed

    Morra, Elena; Giamello, Elio; Van Doorslaer, Sabine; Antinucci, Giuseppe; D'Amore, Maddalena; Busico, Vincenzo; Chiesa, Mario

    2015-04-13

    The typical activation of a fourth generation Ziegler-Natta catalyst TiCl4/MgCl2/phthalate with triethyl aluminum generates Ti(3+) centers that are investigated by multi-frequency continuous wave and pulse EPR methods. Two families of isolated, molecule-like Ti(3+) species have been identified. A comparison of the experimentally derived g tensors and (35,37)Cl hyperfine and nuclear-quadrupole tensors with DFT-computed values suggests that the dominant EPR-active Ti(3+)  species is located on MgCl2(110) surfaces (or equivalent MgCl2 terminations with tetra-coordinated Mg). O2 reactivity tests show that a fraction of these Ti sites is chemically accessible, an important result in view of the search for the true catalyst active site in olefin polymerization. PMID:25706346

  13. Activated microglia mediate axo-glial disruption that contributes to axonal injury in multiple sclerosis

    PubMed Central

    Garg, Anurag; Komada, Masayuki; Brophy, Peter. J.; Reynolds, Richard

    2015-01-01

    The complex symptoms of chronic multiple sclerosis (MS) are due, in part, to widespread axonal pathology affecting lesioned and non-lesioned areas of the CNS. Here we describe an association between microglial activation and axon/ oligodendrocyte pathology at nodal and paranodal domains in normal appearing white matter (NAWM) of MS and experimental allergic encephalomyelitis (EAE). The extent of paranodal axo-glial (neurofascin-155+/Caspr1+) disruption correlated with the local degree of 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 axo-glial alterations were seen in pre-symptomatic EAE, at a time-point characterised by microglia activation prior to the infiltration of immune cells. Disruption of the axo-glial unit in adjuvant immunised animals was reversible and coincided with the resolution of microglial inflammation, whereas paranodal damage and microglial inflammation persisted in chronic EAE. We were able to preserve axo-glial integrity by administering minocycline, which inhibited microglial activation, in actively immunised animals. Therefore, permanent disruption to axo-glial domains in an environment of microglial inflammation is an early indicator of axonal injury that would affect normal nerve conduction contributing to pathology outside of the demyelinated lesion. PMID:20838243

  14. 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

  15. Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis

    PubMed Central

    Klaren, Rachel E.; Hubbard, Elizabeth A.; Motl, Robert W.; Pilutti, Lara A.; Wetter, Nathan C.; Sutton, Bradley P.

    2015-01-01

    Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr = 0.370, p < 0.05), NWMV (pr = 0.433, p < 0.01), hippocampus (pr = 0.499, p < 0.01), thalamus (pr = 0.380, p < 0.05), caudate (pr = 0.539, p < 0.01), putamen (pr = 0.369, p < 0.05), and pallidum (pr = 0.498, p < 0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS. PMID:26146460

  16. Anti-candidal activity of genetically engineered histatin variants with multiple functional domains.

    PubMed

    Oppenheim, Frank G; Helmerhorst, Eva J; Lendenmann, Urs; Offner, Gwynneth D

    2012-01-01

    The human bodily defense system includes a wide variety of innate antimicrobial proteins. Histatins are small molecular weight proteins produced by the human salivary glands that exhibit antifungal and antibacterial activities. While evolutionarily old salivary proteins such as mucins and proline-rich proteins contain large regions of tandem repeats, relatively young proteins like histatins do not contain such repeated domains. Anticipating that domain duplications have a functional advantage, we genetically engineered variants of histatin 3 with one, two, three, or four copies of the functional domain by PCR and splice overlap. The resulting proteins, designated reHst3 1-mer, reHist3 2-mer, reHis3 3-mer and reHist3 4-mer, exhibited molecular weights of 4,062, 5,919, 7,777, and 9,634 Da, respectively. The biological activities of these constructs were evaluated in fungicidal assays toward Candida albicans blastoconidia and germinated cells. The antifungal activities per mole of protein increased concomitantly with the number of functional domains present. This increase, however, was higher than could be anticipated from the molar concentration of functional domains present in the constructs. The demonstrated increase in antifungal activity may provide an evolutionary explanation why such domain multiplication is a frequent event in human salivary proteins. PMID:23251551

  17. 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

  18. 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

  19. 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

  20. Evaluating the Theoretical Content of Online Physical Activity Information for People with Multiple Sclerosis

    PubMed Central

    Baillie, Colin P.T.; Galaviz, Karla; Jarvis, Jocelyn W.; Latimer-Cheung, Amy E.

    2015-01-01

    Background: Physical activity can aid people with multiple sclerosis (MS) in managing symptoms and maintaining functional abilities. The Internet is a preferred source of physical activity information for people with MS and, therefore, a method for the dissemination of behavior change techniques. The purpose of this study was to examine the coverage and quality of physical activity behavior change techniques delivered on the Internet for adults with MS using Abraham and Michie's taxonomy of behavior change techniques. Methods: Using the taxonomy, 20 websites were coded for quality (ie, accuracy of information) and coverage (ie, completeness of information) of theoretical behavior change techniques. Results: Results indicated that most websites covered a mean of 8.05 (SD 3.86, range 3–16) techniques out of a possible 20. Only one of the techniques, provide information on behavior–health link and consequences, was delivered on all websites. The websites demonstrated low mean coverage and quality across all behavior change techniques, with means of 0.64 (SD 0.67) and 0.62 (SD 0.37) on a scale of 0 to 2, respectively. However, coverage and quality improved when websites were examined solely for the techniques that they covered, as opposed to all 20 techniques. Conclusions: This study, which examined quality and coverage of physical activity behavior change techniques described online for people with MS, illustrated that the dissemination of these techniques requires improvement. PMID:25892979