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Sample records for activation state insights

  1. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics.

    Science.gov (United States)

    Bell-Temin, Harris; Culver-Cochran, Ashley E; Chaput, Dale; Carlson, Christina M; Kuehl, Melanie; Burkhardt, Brant R; Bickford, Paula C; Liu, Bin; Stevens, Stanley M

    2015-12-01

    Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells.

  2. Mechanistic insights into heterogeneous methane activation.

    Science.gov (United States)

    Latimer, Allegra A; Aljama, Hassan; Kakekhani, Arvin; Yoo, Jong Suk; Kulkarni, Ambarish; Tsai, Charlie; Garcia-Melchor, Max; Abild-Pedersen, Frank; Nørskov, Jens K

    2017-02-01

    While natural gas is an abundant chemical fuel, its low volumetric energy density has prompted a search for catalysts able to transform methane into more useful chemicals. This search has often been aided through the use of transition state (TS) scaling relationships, which estimate methane activation TS energies as a linear function of a more easily calculated descriptor, such as final state energy, thus avoiding tedious TS energy calculations. It has been shown that methane can be activated via a radical or surface-stabilized pathway, both of which possess a unique TS scaling relationship. Herein, we present a simple model to aid in the prediction of methane activation barriers on heterogeneous catalysts. Analogous to the universal radical TS scaling relationship introduced in a previous publication, we show that a universal TS scaling relationship that transcends catalysts classes also seems to exist for surface-stabilized methane activation if the relevant final state energy is used. We demonstrate that this scaling relationship holds for several reducible and irreducible oxides, promoted metals, and sulfides. By combining the universal scaling relationships for both radical and surface-stabilized methane activation pathways, we show that catalyst reactivity must be considered in addition to catalyst geometry to obtain an accurate estimation for the TS energy. This model can yield fast and accurate predictions of methane activation barriers on a wide range of catalysts, thus accelerating the discovery of more active catalysts for methane conversion.

  3. Insights into Mechanism of Glucokinase Activation

    Science.gov (United States)

    Liu, Shenping; Ammirati, Mark J.; Song, Xi; Knafels, John D.; Zhang, Jeff; Greasley, Samantha E.; Pfefferkorn, Jeffrey A.; Qiu, Xiayang

    2012-01-01

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk. PMID:22298776

  4. Forecasting the solar activity cycle: new insights

    CERN Document Server

    Nandy, Dibyendu

    2013-01-01

    Having advanced knowledge of solar activity is important because the Sun's magnetic output governs space weather and impacts technologies reliant on space. However, the irregular nature of the solar cycle makes solar activity predictions a challenging task. This is best achieved through appropriately constrained solar dynamo simulations and as such the first step towards predictions is to understand the underlying physics of the solar dynamo mechanism. In Babcock-Leighton type dynamo models, the poloidal field is generated near the solar surface whereas the toroidal field is generated in the solar interior. Therefore a finite time is necessary for the coupling of the spatially segregated source layers of the dynamo. This time delay introduces a memory in the dynamo mechanism which allows forecasting of future solar activity. Here we discuss how this forecasting ability of the solar cycle is affected by downward turbulent pumping of magnetic flux. With significant turbulent pumping the memory of the dynamo is ...

  5. Active zone stability: insights from fly neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Xiaolin Tian

    2015-01-01

    Full Text Available The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotransmitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efficacy. However, very little is known about the mechanism that controls the structural stability of active zone. By studying a model synapse, the Drosophila neuromuscular junction, our recent work shed light on how two scaffolding proteins at the active zone regulate active zone stability by promoting a localized dephosphorylation event at the nerve terminal. Here we discuss the major insights from our findings and their implications for future research.

  6. Active zone stability:insights from fly neuromuscular junction

    Institute of Scientific and Technical Information of China (English)

    Xiaolin Tian; Chunlai Wu

    2015-01-01

    The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotrans-mitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efifcacy. However, very little is known about the mechanism that controls the structural stability of active zone. By study-ing a model synapse, theDrosophila neuromuscular junction, our recent work shed light on how two scaffolding proteins at the active zone regulate active zone stability by promoting a localized dephos-phorylation event at the nerve terminal. Here we discuss the major insights from our ifndings and their implications for future research.

  7. Building structure-activity insights through patent mining.

    Science.gov (United States)

    Tu, Meihua; Pfefferkorn, Jeffrey A; Guzman-Perez, Angel; Filipski, Kevin J

    2012-11-01

    One gap in current patent-mining practice is the lack of tools to build SAR knowledge. Here, we report a novel technique that enabled us to derive useful SAR information from the exemplified structures of a series of patents. In our approach, exemplified chemical structures were extracted from patent documents. They were grouped into structural series based on similarity and binding mode, after which the R-group table was generated. By analyzing R-group usages over time, we were able to build insights into SAR of a structural series, even though the biological activities were not available.

  8. Kinetic insights over a PEMFC operating on stationary and oscillatory states.

    Science.gov (United States)

    Mota, Andressa; Gonzalez, Ernesto R; Eiswirth, Markus

    2011-12-01

    Kinetic investigations in the oscillatory state have been carried out in order to shed light on the interplay between the complex kinetics exhibited by a proton exchange membrane fuel cell fed with poisoned H(2) (108 ppm of CO) and the other in serie process. The apparent activation energy (E(a)) in the stationary state was investigated in order to clarify the E(a) observed in the oscillatory state. The apparent activation energy in the stationary state, under potentiostatic control, rendered (a) E(a) ≈ 50-60 kJ mol(-1) over 0.8 V proton conductivity in the membrane. The dependence of the period-one oscillations on the temperature yielded a genuine Arrhenius dependence with two E(a) values: (a) E(a) around 70 kJ mol(-1), at high temperatures, and (b) E(a) around 10-15 kJ mol(-1), at lower temperatures. The latter E(a) indicates the presence of protonic mass transport coupled to the essential oscillatory mechanism. These insights point in the right direction to predict spatial couplings between anode and cathode as having the highest strength as well as to speculate the most likely candidates to promote spatial inhomogeneities.

  9. Insights from simple models for surface states in nanostructures

    Science.gov (United States)

    Boykin, Timothy B.; Klimeck, Gerhard

    2017-03-01

    Surface passivation is of great technological importance due to the increasing miniaturisation of electronic devices. It has been known for many years that under certain conditions surface states can form; when they do so in a quantum well (QW) the result is an unbound (i.e., evanescent) state in the QW. Such surface states are generally undesirable, so a good physical understanding of them is important. A simple single-p-orbital valence band model is used with two types of surface passivation to examine surface states in a QW: (1) an energy upshift added to the terminal atoms; and (2) explicit passivation by an s-orbital on each end of the QW. These models show these unbound/evanescent QW states can occur in both models; that in them the wavefunction is bound to the terminal atoms; and that the existence of these states is connected to the effective valence-band offset between the terminal atoms and the bulk QW.

  10. Insights into correlation between satellite infrared information and fault activities

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Tectonic activities are accompanied with material movement and energy transfer, which definitely change the state of thermal radiation on the ground. Thus it is possible to infer present-day tectonic activities based on variations of the thermal radiation state on the ground. The received satellite infrared information is, however, likely influenced by many kinds of factors. Therefore, the first problem that needs to be solved is to extract information on tectonic activities and eliminate effects of external (non-tectonic) factors. In this study, we firstly make a review of the current studies on this subject, and then present the technical approach and our research goal.Using the data of 20 years from the infrared band of the satellite of National Oceanic and Atmospheric Administration (NOAA) and the method we have developed, we investigate fault activities in western China. The results show that the areas with high residual values of land surface brightness temperature (LSBT), which is presumably related to faultings in space, accord usually with the locations of followed major earthquakes. The times of their value growing are also roughly consistent with the beginning of active periods of earthquakes.The low frequency component fields of the LSBT, acquired from wavelet analysis, exhibit well the spatial distributions of active faults.The "heat penetrability index" (HPI) related with enhancement of subsurface thermal information has been expressed well for the backgrounds of accelerated tectonic motions, and some correlations exist between HPI and the local faulting and seismicity. This study provides a new approach to study temporal-spatial evolution of recent activities of faults and their interactions.

  11. Building Capacity for Tracking Human Capital Development and Its Mobility across State Lines. Policy Insights

    Science.gov (United States)

    Prescott, Brian T.

    2014-01-01

    This issue of "Policy Insights" provides a review of the past five years of the cost and value of higher education, which have gained increased policymaker, consumer, and media attention. The Western Interstate Commission for Higher Education (WICHE) has worked with four of its member states (Hawai'i, Idaho, Oregon, and Washington) to…

  12. Meditation promotes insightful problem-solving by keeping people in a mindful and alert conscious state.

    Science.gov (United States)

    Ren, Jun; Huang, Zhihui; Luo, Jing; Wei, Gaoxia; Ying, Xiaoping; Ding, Zhiguang; Wu, Yibin; Luo, Fei

    2011-10-01

    Although previous studies have shown that sleep can inspire insight, it is still unclear whether meditation can promote insight. Meditation differs from other types of passive rest such as relaxation and sleep because it requires full consciousness and mindfulness of targets such as one's breathing. Forty-eight university students without meditation experience were recruited to learn a simple meditation technique. They were given a list of 10 insight problems to solve (the pre-test session). In this study, we focused on the unsolved problems and examined if they could be successfully solved after a 20 min rest interval with or without meditation. Results showed that relative to the control group that listened to Chinese or English words and made a language judgment, the groups who learned meditation successfully solved significantly more failed problems from the pre-test session, providing direct evidence for the role of meditation in promoting insight. Further analysis showed that maintaining a mindful and alert state during meditation (raising a hand to report every 10 deep breaths compared to every 100 deep breaths) resulted in more insight regarding the failed items from the pre-test session. This implies that it was watchfulness in meditation, rather than relaxation, that actually contributed to insight. Consistently, in the meditation session or control task, the percentage of alpha waves-a brain index of mental relaxation-was negatively correlated with insight. These results suggest a meditation-based insight-promoting mechanism different from that involved in passive rest such as relaxation and sleep.

  13. Improved prediction of RNA tertiary structure with insights into native state dynamics.

    Science.gov (United States)

    Bida, John Paul; Maher, L James

    2012-03-01

    The importance of RNA tertiary structure is evident from the growing number of published high resolution NMR and X-ray crystallographic structures of RNA molecules. These structures provide insights into function and create a knowledge base that is leveraged by programs such as Assemble, ModeRNA, RNABuilder, NAST, FARNA, Mc-Sym, RNA2D3D, and iFoldRNA for tertiary structure prediction and design. While these methods sample native-like RNA structures during simulations, all struggle to capture the native RNA conformation after scoring. We propose RSIM, an improved RNA fragment assembly method that preserves RNA global secondary structure while sampling conformations. This approach enhances the quality of predicted RNA tertiary structure, provides insights into the native state dynamics, and generates a powerful visualization of the RNA conformational space. RSIM is available for download from http://www.github.com/jpbida/rsim.

  14. Interferon Gamma Release Assays in active Tuberculosis: new medical insights

    Directory of Open Access Journals (Sweden)

    Sandro Pierdomenico

    2011-09-01

    Full Text Available Since first presentation, Interferon γ Release Assays (IGRAs have had basic and wide application to LTBI, in accordance with international consensus and CDC recommendations, leaving their use in active TB to the field of study and research.We reviewed the results of 633 patients investigated from 2004 to 2008 targeting active TB, with the objective to highlight immunological data supporting test performances.We evaluated Quantiferon TB Gold (1st generation IGRA kit in association to Culture (MGIT 960 and Lowenstein Jensen and PCR (Probetec-ET having the positivity of culture plus clinical diagnosis as the standard true value to compare. QTB Gold was studied in 69 TB positive patients (42 pulmonary and 27 extra-pulmonary, with Sensitivity, Specificity, PPV and NPV average to 61.8%, 94.5%, 54.3% and 95.9% respectively, after indeterminate results discharging. Significant statistical differences didn’t emerge between pulmonary and extra-pulmonary infections (CI 95%.The overall indeterminate ratio arose up to 20.3% in patients with active TB vs 2.7% of global population (p<0.001. In 22% of patients with active pulmonary disease, IGRA conversed to positivity after 15 days in replicated tests, in spite of current treatment. 4 patients, with pulmonary TB and Quantiferon persistent negativities, underwent 18 months follow-up as not respondent although SIRE phenotypic susceptibilities and enough DOT compliance. Molecular DST documented hetero resistance for rpoB (MUT 1, MUT 3 plus wild lines and katG (MUT 1 plus wild in association to lack of inhA wild lines (Genotype MTBDR plus, Hain Lifescience. These reports suggest a mutational relationship between Rv3874 – 3875 cassette, encoding ESAT-6 / CFP-10, and rpoB, katG, inhA genes plausibly implying weak or absent selective clonal Th 1 activation to IGRA antigens. Our data seem to point out: 1 positive results are able to match true active TB in less than 50% of patients; 2 negative results could leave

  15. An insight into polarization states of solid-state organic lasers

    CERN Document Server

    Gozhyk, I; Meallet-Renault, R; Dvorko, M; Pansu, R; Audibert, J -F; Brosseau, A; Lafargue, C; Tsvirkun, V; Lozenko, S; Forget, S; Chenais, S; Ulysse, C; Zyss, J; Lebental, M

    2012-01-01

    The polarization states of lasers are crucial issues both for practical applications and fundamental research. In general, they depend in a combined manner on the properties of the gain material and on the structure of the electromagnetic modes. In this paper, we address this issue in the case of solid-state organic lasers, a technology which enables to vary independently gain and mode properties. Different kinds of resonators are investigated: in-plane micro-resonators with Fabry-Perot, square, pentagon, stadium, disk, and kite shapes, and external vertical resonators. The degree of polarization P is measured in each case. It is shown that although TE modes prevail generally (P>0), kite-shaped micro-laser generates negative values for P, i.e. a flip of the dominant polarization which becomes mostly TM polarized. We at last investigated two degrees of freedom that are available to tailor the polarization of organic lasers, in addition to the pump polarization and the resonator geometry: upon using resonant en...

  16. Insights into Animal and Plant Lectins with Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Renata de Oliveira Dias

    2015-01-01

    Full Text Available Lectins are multivalent proteins with the ability to recognize and bind diverse carbohydrate structures. The glyco -binding and diverse molecular structures observed in these protein classes make them a large and heterogeneous group with a wide range of biological activities in microorganisms, animals and plants. Lectins from plants and animals are commonly used in direct defense against pathogens and in immune regulation. This review focuses on sources of animal and plant lectins, describing their functional classification and tridimensional structures, relating these properties with biotechnological purposes, including antimicrobial activities. In summary, this work focuses on structural-functional elucidation of diverse lectin groups, shedding some light on host-pathogen interactions; it also examines their emergence as biotechnological tools through gene manipulation and development of new drugs.

  17. Metaproteomics provides functional insight into activated sludge wastewater treatment.

    Directory of Open Access Journals (Sweden)

    Paul Wilmes

    Full Text Available BACKGROUND: Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR. METHODOLOGY/PRINCIPAL FINDINGS: A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism "Candidatus Accumulibacter phosphatis". When EBPR failed, the sludge was dominated by tetrad-forming alpha-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from "Candidatus Accumulibacter phosphatis" and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid beta oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. CONCLUSIONS/SIGNIFICANCE: Importantly, this study provides direct evidence linking the metabolic activities of "Accumulibacter" to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models.

  18. Observation of Andreev bound states at spin-active interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Beckmann, Detlef; Wolf, Michael Johannes [KIT, Institut fuer Nanotechnologie (Germany); Huebler, Florian [KIT, Institut fuer Nanotechnologie (Germany); KIT, Institut fuer Festkoerperphysik (Germany); Loehneysen, Hilbert von [KIT, Institut fuer Festkoerperphysik (Germany); KIT, Physikalisches Institut (Germany)

    2013-07-01

    We report on high-resolution differential conductance experiments on nanoscale superconductor/ferromagnet tunnel junctions with ultra-thin oxide tunnel barriers. We observe subgap conductance features which are symmetric with respect to bias, and shift according to the Zeeman energy with an applied magnetic field. These features can be explained by resonant transport via Andreev bound states induced by spin-active scattering at the interface. From the energy and the Zeeman shift of the bound states, both the magnitude and sign of the spin-dependent interfacial phase shifts between spin-up and spin-down electrons can be determined. These results contribute to the microscopic insight into the triplet proximity effect at spin-active interfaces.

  19. Kinematics Card Sort Activity: Insight into Students' Thinking

    Science.gov (United States)

    Berryhill, Erin; Herrington, Deborah; Oliver, Keith

    2016-12-01

    Kinematics is a topic students are unknowingly aware of well before entering the physics classroom. Students observe motion on a daily basis. They are constantly interpreting and making sense of their observations, unintentionally building their own understanding of kinematics before receiving any formal instruction. Unfortunately, when students take their prior conceptions to understand a new situation, they often do so in a way that inaccurately connects their learning. We were motivated to identify strategies to help our students make accurate connections to their prior knowledge and understand kinematics at a deeper level. To do this, we integrated a formative assessment card sort into a kinematic graphing unit within an introductory high school physics course. Throughout the activities, we required students to document and reflect upon their thinking. This allowed their learning to build upon their own previously held conceptual understanding, which provided an avenue for cognitive growth. By taking a more direct approach to eliciting student reasoning, we hoped to improve student learning and guide our assessment of their learning.

  20. First Versus Second Order Latent Growth Curve Models: Some Insights From Latent State-Trait Theory.

    Science.gov (United States)

    Geiser, Christian; Keller, Brian; Lockhart, Ginger

    2013-07-01

    First order latent growth curve models (FGMs) estimate change based on a single observed variable and are widely used in longitudinal research. Despite significant advantages, second order latent growth curve models (SGMs), which use multiple indicators, are rarely used in practice, and not all aspects of these models are widely understood. In this article, our goal is to contribute to a deeper understanding of theoretical and practical differences between FGMs and SGMs. We define the latent variables in FGMs and SGMs explicitly on the basis of latent state-trait (LST) theory and discuss insights that arise from this approach. We show that FGMs imply a strict trait-like conception of the construct under study, whereas SGMs allow for both trait and state components. Based on a simulation study and empirical applications to the CES-D depression scale (Radloff, 1977) we illustrate that, as an important practical consequence, FGMs yield biased reliability estimates whenever constructs contain state components, whereas reliability estimates based on SGMs were found to be accurate. Implications of the state-trait distinction for the measurement of change via latent growth curve models are discussed.

  1. Insight into the Strong Antioxidant Activity of Deinoxanthin, a Unique Carotenoid in Deinococcus Radiodurans

    OpenAIRE

    Hong-Fang Ji

    2010-01-01

    Deinoxanthin (DX) is a unique carotenoid synthesized by Deinococcus radiodurans, one of the most radioresistant organisms known. In comparison with other carotenoids, DX was proven to exhibit significantly stronger reactive oxygen species (ROS)-scavenging activity, which plays an important role in the radioresistance of D. radiodurans. In this work, to gain deeper insights into the strong antioxidant activity of DX, the parameters characterizing ROS-scavenging potential were calculated by mea...

  2. Political contexts and maternal health policy: insights from a comparison of south Indian states.

    Science.gov (United States)

    Smith, Stephanie L

    2014-01-01

    Nearly 300,000 women die from pregnancy-related complications each year. One-fifth of these deaths occur in India. Maternal survival rose on India's national policy agenda in the mid-2000s, but responsibility for health policy and implementation in the federal system is largely devolved to the state level where priority for the issue and maternal health outcomes vary. This study investigates sources of variation in maternal health policy and implementation sub-nationally in India. The study is guided by four analytical categories drawn from policy process literature: constitutional, governing and social structures; political contexts; actors and ideas. The experiences of two south Indian states-Tamil Nadu a leader and Karnataka a relatively slow mover-are examined. Process-tracing, a case study methodology that helps to identify roles of complex historical events in causal processes, was employed to investigate the research question in each state. The study is informed by interviews with public health policy experts and service delivery professionals, observation of implementation sites and archival document analysis. Historical legacies-Tamil Nadu's non-Brahmin social movement and Karnataka's developmental disparities combined with decentralization-shape the states' political contexts, affecting variation in maternal health policy and implementation. Competition to advance consistent political priorities across regimes in Tamil Nadu offers fertile ground for policy entrepreneurship and strong public health system administration facilitates progress. Inconsistent political priorities and relatively weak public health system administration frustrate progress in Karnataka. These variations offer insights to the ways in which sub-national political and administrative contexts shape health policy and implementation.

  3. New Insights on US Aggregate and State Level Trade with the China Region%New Insights on US Aggregate and State Level Trade with the China Region

    Institute of Scientific and Technical Information of China (English)

    Catherine Y. Co

    2011-01-01

    Aggregate trade data with breakdown into related and non-related party components show that US multinational enterprises use different trading strategies in the China region relative to other countries. US trade with the China region in 2002-007 is characterized by arm 's- length transactions. State-level trade data show great variability in state engagement with the region through trade: exports to the region range from 1 to 28 percent of state exports. In addition, compared to exports to other countries, exports to the region are highly concentrated. At the extreme, for some states, 96-98 percent of exports to the region are computer and electronic products. Finally, gravity regressions show that state exports to Hong Kong are posflively associated with the relative size of the ltong Kong-born population in the states. There is no evidence that stricter labor regimes lead to lower state exports.

  4. Metabolic restructuring during energy-limited states: insights from Artemia franciscana embryos and other animals.

    Science.gov (United States)

    Hand, Steven C; Menze, Michael A; Borcar, Apu; Patil, Yuvraj; Covi, Joseph A; Reynolds, Julie A; Toner, Mehmet

    2011-05-01

    Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ions from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to pre-condition mammalian cells prior to cell biostabilization and storage.

  5. Evolutionary history of assassin bugs (insecta: hemiptera: Reduviidae: insights from divergence dating and ancestral state reconstruction.

    Directory of Open Access Journals (Sweden)

    Wei Song Hwang

    Full Text Available Assassin bugs are one of the most successful clades of predatory animals based on their species numbers (∼6,800 spp. and wide distribution in terrestrial ecosystems. Various novel prey capture strategies and remarkable prey specializations contribute to their appeal as a model to study evolutionary pathways involved in predation. Here, we reconstruct the most comprehensive reduviid phylogeny (178 taxa, 18 subfamilies to date based on molecular data (5 markers. This phylogeny tests current hypotheses on reduviid relationships emphasizing the polyphyletic Reduviinae and the blood-feeding, disease-vectoring Triatominae, and allows us, for the first time in assassin bugs, to reconstruct ancestral states of prey associations and microhabitats. Using a fossil-calibrated molecular tree, we estimated divergence times for key events in the evolutionary history of Reduviidae. Our results indicate that the polyphyletic Reduviinae fall into 11-14 separate clades. Triatominae are paraphyletic with respect to the reduviine genus Opisthacidius in the maximum likelihood analyses; this result is in contrast to prior hypotheses that found Triatominae to be monophyletic or polyphyletic and may be due to the more comprehensive taxon and character sampling in this study. The evolution of blood-feeding may thus have occurred once or twice independently among predatory assassin bugs. All prey specialists evolved from generalist ancestors, with multiple evolutionary origins of termite and ant specializations. A bark-associated life style on tree trunks is ancestral for most of the lineages of Higher Reduviidae; living on foliage has evolved at least six times independently. Reduviidae originated in the Middle Jurassic (178 Ma, but significant lineage diversification only began in the Late Cretaceous (97 Ma. The integration of molecular phylogenetics with fossil and life history data as presented in this paper provides insights into the evolutionary history of

  6. Further insight into mechanisms of solid-state interactions in UMo/Al system

    Science.gov (United States)

    Mazaudier, F.; Proye, C.; Hodaj, F.

    2008-07-01

    In this paper, the solid-state interactions between metastable γ-UMo alloys (containing 5, 7 and 10 wt%Mo) and Al, at temperatures ranging from 440 to 600 °C and for ageing times up to 10 h, are studied using the diffusion couple technique and nuclear fuel plate annealing. The reaction product consists of three main zones, two of them presenting a periodic layered morphology. The growth kinetics is limited by solid-state diffusion and Al is the most mobile species. Both growth kinetics and its global energy of activation are similar to that found for the U/Al binary system. The diffusion path is determined and phase equilibrium relations are deduced for the Mo-poor part of the U-Mo-Al metastable ternary phase diagram.

  7. Insight in Psychiatry and Neurology: State of the Art, and Hypotheses.

    Science.gov (United States)

    Landi, Paola; Marazziti, Donatella; Rutigliano, Grazia; Dell'Osso, Liliana

    2016-01-01

    In spite of the increasing number of studies on insight in psychiatry and also in neurology and psychology, its nature is still elusive. It encompasses at least three fundamental characteristics: the awareness of suffering from an illness, an understanding of the cause and source of this suffering, and an acknowledgment of the need for treatment. As such, insight is fundamental for patients' management, prognosis, and treatment. Not surprisingly, the majority of available data, which have been gathered on schizophrenia, show a relationship between low insight and poorer outcomes. For mood disorders, however, insight is associated with less positive results. For other psychiatric disorders, insight has rarely been investigated. In neurology, the impaired ability to recognize the presence of sensory, perceptual, motor, affective, or cognitive functioning-referred to as anosognosia-has been related to damage of specific brain regions. This article provides a comprehensive review of insight in different psychiatric and neurological disorders, with a special focus on brain areas and neurotransmitters that serve as the substrate for this complex phenomenon.

  8. An insight into the process and mechanism of a mechanically activated reaction for synthesizing AlH3 nano-composites.

    Science.gov (United States)

    Duan, Congwen; Hu, Lianxi; Sun, Yu; Zhou, Haiping; Yu, Huan

    2015-10-07

    The reaction pathway as well as the mechanism of the solid state reaction between MgH2 and AlCl3 has been a mystery so far. Based on SEM, TEM and NMR (Nuclear Magnetic Resonance) analyses, an amorphous intermediate (AlH6)n was preferentially formed and recrystallized as a γ phase at the final stage of the reaction. As a novel finding, this research provides a deep insight into the process and mechanism of this mechanically activated reaction.

  9. Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1.

    Science.gov (United States)

    Wei, Risheng; Wang, Xue; Zhang, Yan; Mukherjee, Saptarshi; Zhang, Lei; Chen, Qiang; Huang, Xinrui; Jing, Shan; Liu, Congcong; Li, Shuang; Wang, Guangyu; Xu, Yaofang; Zhu, Sujie; Williams, Alan J; Sun, Fei; Yin, Chang-Cheng

    2016-09-01

    Ryanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca(2+)-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 Å and a resolution of 4.2 Å for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca(2+) activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family.

  10. Insight into the strong antioxidant activity of deinoxanthin, a unique carotenoid in Deinococcus radiodurans.

    Science.gov (United States)

    Ji, Hong-Fang

    2010-11-10

    Deinoxanthin (DX) is a unique carotenoid synthesized by Deinococcus radiodurans, one of the most radioresistant organisms known. In comparison with other carotenoids, DX was proven to exhibit significantly stronger reactive oxygen species (ROS)-scavenging activity, which plays an important role in the radioresistance of D. radiodurans. In this work, to gain deeper insights into the strong antioxidant activity of DX, the parameters characterizing ROS-scavenging potential were calculated by means of quantum chemical calculations. It was found that DX possesses lower lowest triplet excitation energy for its unique structure than other carotenoids, such as β-carotene and zeaxanthin, which endows DX strong potential in the energy transfer-based ROS-scavenging process. Moreover, the H-atom donating potential of DX is similar to zeaxanthin according to the theoretical homolytic O-H bond dissociation enthalpy. Thus, the large number of conjugated double bonds should be crucial for its strong antioxidant activity.

  11. Insight into the Strong Antioxidant Activity of Deinoxanthin, a Unique Carotenoid in Deinococcus Radiodurans

    Directory of Open Access Journals (Sweden)

    Hong-Fang Ji

    2010-11-01

    Full Text Available Deinoxanthin (DX is a unique carotenoid synthesized by Deinococcus radiodurans, one of the most radioresistant organisms known. In comparison with other carotenoids, DX was proven to exhibit significantly stronger reactive oxygen species (ROS-scavenging activity, which plays an important role in the radioresistance of D. radiodurans. In this work, to gain deeper insights into the strong antioxidant activity of DX, the parameters characterizing ROS-scavenging potential were calculated by means of quantum chemical calculations. It was found that DX possesses lower lowest triplet excitation energy for its unique structure than other carotenoids, such as β-carotene and zeaxanthin, which endows DX strong potential in the energy transfer-based ROS‑scavenging process. Moreover, the H-atom donating potential of DX is similar to zeaxanthin according to the theoretical homolytic O-H bond dissociation enthalpy. Thus, the large number of conjugated double bonds should be crucial for its strong antioxidant activity.

  12. Widely available active sites on Ni2P for electrochemical hydrogen evolution - insights from first principles calculations

    DEFF Research Database (Denmark)

    Hansen, Martin Hangaard; Stern, Lucas-Alexandre; Feng, Ligang;

    2015-01-01

    We present insights into the mechanism and the active site for hydrogen evolution on nickel phosphide (Ni2P). Ni2P was recently discovered to be a very active non-precious hydrogen evolution catalyst. Current literature attributes the activity of Ni2P to a particular site on the (0001) facet. In ...

  13. Insights about Fall Prevention of Older Adults in the State of Hawai‘i

    Science.gov (United States)

    Hayashida, Cullen T; Yontz, Valerie

    2017-01-01

    The senior population in Hawai‘i is growing at a dramatic pace. In the older population, falls and fall-related injuries are leading causes of morbidity and mortality. Moreover, the health care costs for falls are very high. The State of Hawai‘i has taken measures to prevent falls through the promotion of medication reviews, vision checks, home assessments, and exercise. However, current published examinations of fall preventive measures have been insufficient, and more research is needed to confirm risk factors, effectiveness of preventive measures, and to explore future objectives. This paper examined the validity of fall risk factors and fall preventive measures for Hawai‘i's seniors by conducting mail questionnaire surveys to a sample of seniors using medical alert services from one company in Hawai‘i. The results of chi-square analysis suggest that having reduced ability to perform Activities of Daily Living (ADL) and reduced Instrumental Activities of Daily Living (IADL) were associated with a greater risk of falls (P IADL. Furthermore, the results suggest that seniors do not accept that they are at risk of falling before they actually fall. Public health providers should consider how they approach seniors, and how they inform them of the importance of fall prevention across the life span. PMID:28090397

  14. The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly

    Science.gov (United States)

    Mainwaring, David E.; Nguyen, Song Ha; Webb, Hayden; Jakubov, Timur; Tobin, Mark; Lamb, Robert N.; Wu, Alex H.-F.; Marchant, Richard; Crawford, Russell J.; Ivanova, Elena P.

    2016-03-01

    While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron

  15. Insights and models from medical anthropology for understanding the healing activity of the Historical Jesus

    Directory of Open Access Journals (Sweden)

    John J. Pilch

    1995-01-01

    Full Text Available This essay sketches a basic introdution to medical anthropology as a key to understanding and interpreting  the healing activity of the historical Jesus described in the gospels. It presents select literature, leading experts, fundamental concepts, and insights and models of special value to biblical specialists. Only a cross-cultural discipline like medical anthropology allows the investigator to  interpret texts and events from other cultures with respect for their distinctive cultural contexts in order to draw more appropriate conclusions and applications in other cultures. Applications to biblical texts are not included in this essay but may be found in other articles published by the author and listed in the bibliography.

  16. Structural insights into the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of ceftobiprole.

    Science.gov (United States)

    Lovering, Andrew L; Gretes, Michael C; Safadi, Susan S; Danel, Franck; de Castro, Liza; Page, Malcolm G P; Strynadka, Natalie C J

    2012-09-14

    Methicillin-resistant Staphylococcus aureus (MRSA) is an antibiotic-resistant strain of S. aureus afflicting hospitals and communities worldwide. Of greatest concern is its development of resistance to current last-line-of-defense antibiotics; new therapeutics are urgently needed to combat this pathogen. Ceftobiprole is a recently developed, latest generation cephalosporin and has been the first to show activity against MRSA by inhibiting essential peptidoglycan transpeptidases, including the β-lactam resistance determinant PBP2a, from MRSA. Here we present the structure of the complex of ceftobiprole bound to PBP2a. This structure provides the first look at the molecular details of an effective β-lactam-resistant PBP interaction, leading to new insights into the mechanism of ceftobiprole efficacy against MRSA.

  17. The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly.

    Science.gov (United States)

    Mainwaring, David E; Nguyen, Song Ha; Webb, Hayden; Jakubov, Timur; Tobin, Mark; Lamb, Robert N; Wu, Alex H-F; Marchant, Richard; Crawford, Russell J; Ivanova, Elena P

    2016-03-28

    While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.

  18. Commentary on the Liquid Metallic Hydrogen Model of the Sun: Insight Relative to Coronal Holes, Sunspots, and Solar Activity

    Directory of Open Access Journals (Sweden)

    Robitaille P.-M.

    2013-04-01

    Full Text Available While mankind will always remain unable to sample the interior of the Sun, the presence of sunspots and coronal holes can provide clues as to its subsurface structure. Insight relative to the solar body can also be gained by recognizing that the Sun must exist in the condensed state and support a discrete lattice structure, as required for the production of its continuous spectrum. In this regard, the layered liquid metallic hydrogen lattice advanced as a condensed model of the Sun (Robitaille P.M. Liquid Metallic Hydrogen: A Building Block for the Liquid Sun. Progr. Phys ., 2011, v. 3, 60–74; Robitaille P.M. Liquid Metallic Hydrogen II: A Critical Assessment of Current and Primordial Helium Levels in Sun. Progr. Phys ., 2013, v. 2, 35–47; Robitaille J.C. and Robitaille P.M. Liquid Metallic Hydrogen III. Intercalation and Lattice Exclusion Versus Gravitational Settling and Their Consequences Relative to Internal Structure, Surface Activity, and Solar Winds in the Sun. Progr. Phys ., 2013, v. 2, in press provides the ability to add structure to the solar interior. This constitutes a significant advantage over the gaseous solar models. In fact, a layered liquid metallic hydrogen lattice and the associated intercalation of non-hydrogen elements can help to account for the position of sunspots and coronal holes. At the same time, this model provides a greater understanding of the mechanisms which drive solar winds and activity.

  19. Insights into partially folded or unfolded States of metalloproteins from nuclear magnetic resonance.

    Science.gov (United States)

    Turano, Paola

    2004-12-13

    Nuclear magnetic resonance (NMR) provides detailed insights into the conformational features of unfolded and partially folded proteins. In the case of metalloproteins, special attention should be devoted to the characterization of the properties of the metal binding sites, and specific approaches need to be developed depending on the nature of the metal ion and its coordination environment. At the same time, metal-based NMR parameters may help in getting a better picture of the average structural properties of the metalloprotein. A critical evaluation of the limits of applicability of paramagnetic effects for solution structure determination in partially folded or unfolded proteins is presented. The coupling between NMR characterization of structure and dynamic of the polypeptide chain and of the metal environment provides insights into the stabilizing role of metal ions in metalloproteins. The overall approach is illustrated for some case examples of increasing flexibility obtained far from native conditions for cytochrome c and superoxide dismutase, two metalloproteins that have been extensively studied in our lab and whose misfolded forms may be relevant for important biological processes.

  20. Excited state decay of cyclometalated polypyridine ruthenium complexes: insight from theory and experiment.

    Science.gov (United States)

    Kreitner, Christoph; Heinze, Katja

    2016-09-21

    Deactivation pathways of the triplet metal-to-ligand charge transfer ((3)MLCT) excited state of cyclometalated polypyridine ruthenium complexes with [RuN5C](+) coordination are discussed on the basis of the available experimental data and a series of density functional theory calculations. Three different complex classes are considered, namely with [Ru(N^N)2(N^C)](+), [Ru(N^N^N)(N^C^N)](+) and [Ru(N^N^N)(N^N^C)](+) coordination modes. Excited state deactivation in these complex types proceeds via five distinct decay channels. Vibronic coupling of the (3)MLCT state to high-energy oscillators of the singlet ground state ((1)GS) allows tunneling to the ground state followed by vibrational relaxation (path A). A ligand field excited state ((3)MC) is thermally accessible via a (3)MLCT →(3)MC transition state with the (3)MC state being strongly coupled to the (1)GS surface via a low-energy minimum energy crossing point (path B). Furthermore, a (3)MLCT →(1)GS surface crossing point directly couples the triplet and singlet potential energy surfaces (path C). Charge transfer states either with higher singlet character or with different orbital parentage and intrinsic symmetry restrictions are thermally populated which promote non-radiative decay via tunneling to the (1)GS state (path D). Finally, the excited state can decay via phosphorescence (path E). The dominant deactivation pathways differ for the three individual complex classes. The implications of these findings for isoelectronic iridium(iii) or iron(ii) complexes are discussed. Ultimately, strategies for optimizing the emission efficiencies of cyclometalated polypyridine complexes of d(6)-metal ions, especially Ru(II), are suggested.

  1. Charge-Transfer Excited States in Aqueous DNA: Insights from Many-Body Green's Function Theory

    Science.gov (United States)

    Yin, Huabing; Ma, Yuchen; Mu, Jinglin; Liu, Chengbu; Rohlfing, Michael

    2014-06-01

    Charge-transfer (CT) excited states play an important role in the excited-state dynamics of DNA in aqueous solution. However, there is still much controversy on their energies. By ab initio many-body Green's function theory, together with classical molecular dynamics simulations, we confirm the existence of CT states at the lower energy side of the optical absorption maximum in aqueous DNA as observed in experiments. We find that the hydration shell can exert strong effects (˜1 eV) on both the electronic structure and CT states of DNA molecules through dipole electric fields. In this case, the solvent cannot be simply regarded as a macroscopic screening medium as usual. The influence of base stacking and base pairing on the CT states is also discussed.

  2. Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

    DEFF Research Database (Denmark)

    Rasmussen, Søren Gøgsig Faarup; Choi, Hee-Jung; Fung, Juan Jose;

    2011-01-01

    G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due...... to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex....... Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those...

  3. B-H bond activation using an electrophilic metal complex: insights into the reaction pathway.

    Science.gov (United States)

    Kumar, Rahul; Jagirdar, Balaji R

    2013-01-07

    A highly electrophilic ruthenium center in the [RuCl(dppe)(2)][OTf] complex brings about the activation of the B-H bond in ammonia borane (H(3)N·BH(3), AB) and dimethylamine borane (Me(2)HN·BH(3), DMAB). At room temperature, the reaction between [RuCl(dppe)(2)][OTf] and AB or DMAB results in trans-[RuH(η(2)-H(2))(dppe)(2)][OTf], trans-[RuCl(η(2)-H(2))(dppe)(2)][OTf], and trans-[RuH(Cl)(dppe)(2)], as noted in the NMR spectra. Mixing the ruthenium complex and AB or DMAB at low temperature (198/193 K) followed by NMR spectral measurements as the reaction mixture was warmed up to room temperature allowed the observation of various species formed enroute to the final products that were obtained at room temperature. On the basis of the variable-temperature multinuclear NMR spectroscopic studies of these two reactions, the mechanistic insights for B-H bond activation were obtained. In both cases, the reaction proceeds via an η(1)-B-H moiety bound to the metal center. The detailed mechanistic pathways of these two reactions as studied by NMR spectroscopy are described.

  4. Structural insights into Cydia pomonella pheromone binding protein 2 mediated prediction of potentially active semiochemicals

    Science.gov (United States)

    Tian, Zhen; Liu, Jiyuan; Zhang, Yalin

    2016-03-01

    Given the advantages of behavioral disruption application in pest control and the damage of Cydia pomonella, due progresses have not been made in searching active semiochemicals for codling moth. In this research, 31 candidate semiochemicals were ranked for their binding potential to Cydia pomonella pheromone binding protein 2 (CpomPBP2) by simulated docking, and this sorted result was confirmed by competitive binding assay. This high predicting accuracy of virtual screening led to the construction of a rapid and viable method for semiochemicals searching. By reference to binding mode analyses, hydrogen bond and hydrophobic interaction were suggested to be two key factors in determining ligand affinity, so is the length of molecule chain. So it is concluded that semiochemicals of appropriate chain length with hydroxyl group or carbonyl group at one head tended to be favored by CpomPBP2. Residues involved in binding with each ligand were pointed out as well, which were verified by computational alanine scanning mutagenesis. Progress made in the present study helps establish an efficient method for predicting potentially active compounds and prepares for the application of high-throughput virtual screening in searching semiochemicals by taking insights into binding mode analyses.

  5. States of consciousness experimental insights into meditation, waking, sleep and dreams

    CERN Document Server

    Cvetkovic, Dean

    2011-01-01

    In this accessible overview of current knowledge, an expert team of editors and authors describe experimental approaches to consciousness. These approaches are shedding light on some of the hitherto unknown aspects of the distinct states of human consciousness, including the waking state, different states of sleep and dreaming, meditation and more. The book presents the latest research studies by the contributing authors, whose specialities span neuroscience, neurology, biomedical engineering, clinical psychology and psychophysiology, psychosocial medicine and anthropology. Overall this anthology provides the reader with a clear picture of how different states of consciousness can be defined, experimentally measured and analysed. A future byproduct of this knowledge may be anticipated in the development of systematic corrective treatments for many disorders and pathological problems of consciousness.

  6. Validity Evidence for the State Mindfulness Scale for Physical Activity

    Science.gov (United States)

    Cox, Anne E.; Ullrich-French, Sarah; French, Brian F.

    2016-01-01

    Being attentive to and aware of one's experiences in the present moment with qualities of acceptance and openness reflects the state of mindfulness. Positive associations exist between state mindfulness and state autonomous motivation for everyday activities. Though this suggests that state mindfulness links with adaptive motivational experiences,…

  7. Dynamical insights into (1)pi sigma(*) state mediated photodissociation of aniline.

    Science.gov (United States)

    King, Graeme A; Oliver, Thomas A A; Ashfold, Michael N R

    2010-06-07

    This article reports a comprehensive study of the mechanisms of H atom loss in aniline (C(6)H(5)NH(2)) following ultraviolet excitation, using H (Rydberg) atom photofragment translational spectroscopy. N-H bond fission via the low lying (1)pi sigma(*) electronic state of aniline is experimentally demonstrated. The (1)pi sigma(*) potential energy surface (PES) of this prototypical aromatic amine is essentially repulsive along the N-H stretch coordinate, but possesses a shallow potential well in the vertical Franck-Condon region, supporting quasibound vibrational levels. Photoexcitation at wavelengths (lambda(phot)) in the range 293.859 nm > or = lambda(phot) > or = 193.3 nm yields H atom loss via a range of mechanisms. With lambda(phot) resonant with the 1(1)pi pi(*) resonantly enhanced at the one photon energy by the first (1)pi pi(*) excited state (the 1(1)pi pi(*) state). Direct excitation to the first few quasibound vibrational levels of the (1)pi sigma(*) state (at wavelengths in the range 269.513 nm > or = lambda(phot) > or = 260 nm) induces N-H bond fission via H atom tunneling through an exit barrier into the repulsive region of the (1)pi sigma(*) PES, forming anilino (C(6)H(5)NH) radical products in their ground electronic state, and with very limited vibrational excitation; the photo-prepared vibrational mode in the (1)pi sigma(*) state generally evolves adiabatically into the corresponding mode of the anilino radical upon dissociation. However, as the excitation wavelength is reduced (lambda(phot) conical intersection. Changes in product kinetic energy disposal once lambda(phot) approaches approximately 230 nm likely indicate that the photodissociation pathways of aniline proceed via direct excitation to the (higher) 2(1)pi pi(*) state. Analysis of the anilino fragment vibrational energy disposal-and thus the concomitant dynamics of (1)pi sigma(*) state mediated photodissociation-provides a particularly interesting study of competing sigma(*) <-- pi and

  8. Active Affordance Learning in Continuous State and Action Spaces

    NARCIS (Netherlands)

    Wang, C.; Hindriks, K.V.; Babuska, R.

    2014-01-01

    Learning object affordances and manipulation skills is essential for developing cognitive service robots. We propose an active affordance learning approach in continuous state and action spaces without manual discretization of states or exploratory motor primitives. During exploration in the action

  9. Magnetic latitude dependence of oxygen charge states in the global magnetosphere: Insights into solar wind-originating ion injection

    Science.gov (United States)

    Allen, R. C.; Livi, S. A.; Vines, S. K.; Goldstein, J.

    2016-10-01

    Understanding the sources and subsequent evolution of plasma in a magnetosphere holds intrinsic importance for magnetospheric dynamics. Previous studies have investigated the balance of ionospheric-originating heavy ions (low charge state) from those of solar wind origin (high charge state) in the magnetosphere of Earth. These studies have suggested a variety of entry mechanisms for solar wind ions to penetrate into the magnetosphere. Following from recently published distributions for oxygen charge states observed by the Polar spacecraft, this paper investigates oxygen charge state flux distributions versus L shell and magnetic latitude. By showing these distributions in this frame, and binning by various proxies for magnetospheric dynamics (Dst, AE, VSW∗BZ, Pdyn), insight has been gained into the underlying physics at play for oxygen injection. Ionospheric-originating oxygen is observed to depend predominantly on Dst, whereas solar wind-originating oxygen is observed to have a strong dependence on solar wind dynamic pressure (Pdyn) at the flanks and on VSW∗BZ at the dayside. This suggests that both Kelvin-Helmholtz instabilities and reconnection play major roles in solar wind ion penetration into a magnetosphere. Additionally, the near-Earth magnetotail reconnection site does not seem to be a major injection site of solar wind-originating plasma in the 1 to 200 keV/e energy range.

  10. New insight and old dilemma: a cross-cultural comparison of Japan and the United States.

    Science.gov (United States)

    Lebra, T S

    2000-01-01

    Conflict in close relationships, or "generative tension," characterizes both the United States and Japan, with differences only in the style and timing of its manifestation. The potentially fruitful strategy of Rothbaum et al.'s article is constrained by their cross-cultural comparative methodology.

  11. Request Strategies in Professional E-Mail Correspondence: Insights from the United States Workplace

    Science.gov (United States)

    Leopold, Lisa

    2015-01-01

    Despite growing interest in the rhetorical features of e-mail correspondence, this is the first study to examine the request strategies in e-mails written by native English-speaking professionals from a variety of industries in the United States. This study uses Blum-Kulka, House, and Kasper's (1989) speech act framework to analyze the request…

  12. Seismic amplification within the Seattle Basin, Washington State: Insights from SHIPS seismic tomography experiments

    Science.gov (United States)

    Snelson, C.M.; Brocher, T.M.; Miller, K.C.; Pratt, T.L.; Trehu, A.M.

    2007-01-01

    Recent observations indicate that the Seattle sedimentary basin, underlying Seattle and other urban centers in the Puget Lowland, Washington, amplifies long-period (1-5 sec) weak ground motions by factors of 10 or more. We computed east-trending P- and S-wave velocity models across the Seattle basin from Seismic Hazard Investigations of Puget Sound (SHIPS) experiments to better characterize the seismic hazard the basin poses. The 3D tomographic models, which resolve features to a depth of 10 km, for the first time define the P- and S-wave velocity structure of the eastern end of the basin. The basin, which contains sedimentary rocks of Eocene to Holocene, is broadly symmetric in east-west section and reaches a maximum thickness of 6 km along our profile beneath north Seattle. A comparison of our velocity model with coincident amplification curves for weak ground motions produced by the 1999 Chi-Chi earthquake suggests that the distribution of Quaternary deposits and reduced velocity gradients in the upper part of the basement east of Seattle have significance in forecasting variations in seismic-wave amplification across the basin. Specifically, eastward increases in the amplification of 0.2- to 5-Hz energy correlate with locally thicker unconsolidated deposits and a change from Crescent Formation basement to pre-Tertiary Cascadia basement. These models define the extent of the Seattle basin, the Seattle fault, and the geometry of the basement contact, giving insight into the tectonic evolution of the Seattle basin and its influence on ground shaking.

  13. Mechanochemical coupling in the myosin motor domain. I. Insights from equilibrium active-site simulations.

    Directory of Open Access Journals (Sweden)

    Haibo Yu

    2007-02-01

    Full Text Available Although the major structural transitions in molecular motors are often argued to couple to the binding of Adenosine triphosphate (ATP, the recovery stroke in the conventional myosin has been shown to be dependent on the hydrolysis of ATP. To obtain a clearer mechanistic picture for such "mechanochemical coupling" in myosin, equilibrium active-site simulations with explicit solvent have been carried out to probe the behavior of the motor domain as functions of the nucleotide chemical state and conformation of the converter/relay helix. In conjunction with previous studies of ATP hydrolysis with different active-site conformations and normal mode analysis of structural flexibility, the results help establish an energetics-based framework for understanding the mechanochemical coupling. It is proposed that the activation of hydrolysis does not require the rotation of the lever arm per se, but the two processes are tightly coordinated because both strongly couple to the open/close transition of the active site. The underlying picture involves shifts in the dominant population of different structural motifs as a consequence of changes elsewhere in the motor domain. The contribution of this work and the accompanying paper [] is to propose the actual mechanism behind these "population shifts" and residues that play important roles in the process. It is suggested that structural flexibilities at both the small and large scales inherent to the motor domain make it possible to implement tight couplings between different structural motifs while maintaining small free-energy drops for processes that occur in the detached states, which is likely a feature shared among many molecular motors. The significantly different flexibility of the active site in different X-ray structures with variable level arm orientations supports the notation that external force sensed by the lever arm may transmit into the active site and influence the chemical steps (nucleotide

  14. UP states protect ongoing cortical activity from thalamic inputs.

    Directory of Open Access Journals (Sweden)

    Brendon O Watson

    Full Text Available Cortical neurons in vitro and in vivo fluctuate spontaneously between two stable membrane potentials: a depolarized UP state and a hyperpolarized DOWN state. UP states temporally correspond with multineuronal firing sequences which may be important for information processing. To examine how thalamic inputs interact with ongoing cortical UP state activity, we used calcium imaging and targeted whole-cell recordings of activated neurons in thalamocortical slices of mouse somatosensory cortex. Whereas thalamic stimulation during DOWN states generated multineuronal, synchronized UP states, identical stimulation during UP states had no effect on the subthreshold membrane dynamics of the vast majority of cells or on ongoing multineuronal temporal patterns. Both thalamocortical and corticocortical PSPs were significantly reduced and neuronal input resistance was significantly decreased during cortical UP states -- mechanistically consistent with UP state insensitivity. Our results demonstrate that cortical dynamics during UP states are insensitive to thalamic inputs.

  15. Insights into the conformation of aminofluorene-deoxyguanine adduct in a DNA polymerase active site.

    Science.gov (United States)

    Vaidyanathan, Vaidyanathan G; Liang, Fengting; Beard, William A; Shock, David D; Wilson, Samuel H; Cho, Bongsup P

    2013-08-09

    The active site conformation of the mutagenic fluoroaminofluorene-deoxyguanine adduct (dG-FAF, N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene) has been investigated in the presence of Klenow fragment of Escherichia coli DNA polymerase I (Kfexo(-)) and DNA polymerase β (pol β) using (19)F NMR, insertion assay, and surface plasmon resonance. In a single nucleotide gap, the dG-FAF adduct adopts both a major-groove- oriented and base-displaced stacked conformation, and this heterogeneity is retained upon binding pol β. The addition of a non-hydrolysable 2'-deoxycytosine-5'-[(α,β)-methyleno]triphosphate (dCMPcPP) nucleotide analog to the binary complex results in an increase of the major groove conformation of the adduct at the expense of the stacked conformation. Similar results were obtained with the addition of an incorrect dAMPcPP analog but with formation of the minor groove binding conformer. In contrast, dG-FAF adduct at the replication fork for the Kfexo(-) complex adopts a mix of the major and minor groove conformers with minimal effect upon the addition of non-hydrolysable nucleotides. For pol β, the insertion of dCTP was preferred opposite the dG-FAF adduct in a single nucleotide gap assay consistent with (19)F NMR data. Surface plasmon resonance binding kinetics revealed that pol β binds tightly with DNA in the presence of correct dCTP, but the adduct weakens binding with no nucleotide specificity. These results provide molecular insights into the DNA binding characteristics of FAF in the active site of DNA polymerases and the role of DNA structure and sequence on its coding potential.

  16. Dynamical insights into 1πσ* state mediated photodissociation of aniline

    Science.gov (United States)

    King, Graeme A.; Oliver, Thomas A. A.; Ashfold, Michael N. R.

    2010-06-01

    This article reports a comprehensive study of the mechanisms of H atom loss in aniline (C6H5NH2) following ultraviolet excitation, using H (Rydberg) atom photofragment translational spectroscopy. N-H bond fission via the low lying π1σ∗ electronic state of aniline is experimentally demonstrated. The π1σ∗ potential energy surface (PES) of this prototypical aromatic amine is essentially repulsive along the N-H stretch coordinate, but possesses a shallow potential well in the vertical Franck-Condon region, supporting quasibound vibrational levels. Photoexcitation at wavelengths (λphot) in the range 293.859 nm≥λphot≥193.3 nm yields H atom loss via a range of mechanisms. With λphot resonant with the 1π1π∗←S0 origin (293.859 nm), H atom loss proceeds via, predominantly, multiphoton excitation processes, resonantly enhanced at the one photon energy by the first π1π∗ excited state (the 1π1π∗ state). Direct excitation to the first few quasibound vibrational levels of the π1σ∗ state (at wavelengths in the range 269.513 nm≥λphot≥260 nm) induces N-H bond fission via H atom tunneling through an exit barrier into the repulsive region of the π1σ∗ PES, forming anilino (C6H5NH) radical products in their ground electronic state, and with very limited vibrational excitation; the photo-prepared vibrational mode in the π1σ∗ state generally evolves adiabatically into the corresponding mode of the anilino radical upon dissociation. However, as the excitation wavelength is reduced (λphot<260 nm), N-H bond fission yields fragments with substantially greater vibrational excitation, rationalized in terms of direct excitation to 1π1π∗ levels, followed by coupling to the π1σ∗ PES via a 1π1π∗/π1σ∗ conical intersection. Changes in product kinetic energy disposal once λphot approaches ˜230 nm likely indicate that the photodissociation pathways of aniline proceed via direct excitation to the (higher) 2π1π∗ state. Analysis of the

  17. Solid-state NMR in macromolecular systems: insights on how molecular entities move.

    Science.gov (United States)

    Hansen, Michael Ryan; Graf, Robert; Spiess, Hans Wolfgang

    2013-09-17

    The function of synthetic and natural macromolecularsystems critically depends on the packing and dynamics of the individual components of a given system. Not only can solid-state NMR provide structural information with atomic resolution, but it can also provide a way to characterize the amplitude and time scales of motions over broad ranges of length and time. These movements include molecular dynamics, rotational and translational motions of the building blocks, and also the motion of the functional species themselves, such as protons or ions. This Account examines solid-state NMR methods for correlating dynamics and function in a variety of chemical systems. In the early days, scientists thought that the rotationalmotions reflected the geometry of the moving entities. They described these phenomena as jumps about well-defined axes, such as phenyl flips, even in amorphous polymers. Later, they realized that conformational transitions in macromolecules happen in a much more complex way. Because the individual entities do not rotate around well-defined axes, they require much less space. Only recently researchers have appreciated the relative importance of large angle fluctuations of polymers over rotational jumps. Researchers have long considered that cooperative motions might be at work, yet only recently they have clearly detected these motions by NMR in macromolecular and supramolecular systems. In correlations of dynamics and function, local motions do not always provide the mechanism of long-range transport. This idea holds true in ion conduction but also applies to chain transport in polymer melts and semicrystalline polymers. Similar chain motions and ion transport likewise occur in functional biopolymers, systems where solid-state NMR studies are also performed. In polymer science, researchers have appreciated the unique information on molecular dynamics available from advanced solid-state NMR at times, where their colleagues in the biomacromolecular

  18. Secondary School Journalism in the United States. Indiana High School Journalism Institute Insight. Research Report.

    Science.gov (United States)

    Dvorak, Jack

    A study investigated media-related activities in U.S. secondary schools. A seven-page survey was completed by 834 high school personnel from around the country. Topics addressed included the extent and type of media outlets and classes; journalism credit; recruitment of students; participation by students from multicultural backgrounds; and the…

  19. From REM sleep behaviour disorder to status dissociatus: insights into the maze of states of being.

    Science.gov (United States)

    Vetrugno, Roberto; Montagna, Pasquale

    2011-12-01

    Sleep is a coordinated process involving more or less simultaneous changes in sensory, motor, autonomic, hormonal, and cerebral processes. On the other hand, none of the changes occurring with sleep are invariably coupled to sleep. EEG synchrony, heat loss, sleep-related hormone secretion, and even REM-related motoneuron paralysis may occur independent of the parent state. In REM sleep behaviour disorder (RBD) the muscle tone of wakefulness intrudes into REM sleep, allowing the release of dream-enacting behaviours. Status dissociatus (SD) is a condition in which brain and mind are in disarray along the boundaries of sleep and wakefulness. The existence of such dissociated behaviours shows that they have separate neuronal control systems and indicates that the whole organization of sleep is an emergent property of the collective neuronal systems to synchronize. Insults to the brain can drastically alter the circuitries responsible for maintaining the integrity of wakefulness, NREM sleep, and REM sleep. As a consequence, the basic states of existence can become admixed and interchanged with striking disturbances of consciousness, brain electrophysiology, and the behavioural and polygraphic expression of sleep and wakefulness. The evolution of RBD into SD may result from a disarray of (brainstem) structures that orchestrate the whole brain wake-sleep conditions, but with preserved discrete systems and dissociable strategies to still place navigation in wake and sleep. Advances in the fields of genetics, neuroimaging, and behavioural neurology will expand the understanding of the mechanisms underlying the organization of the states of being along with their somatic/behavioural manifestations.

  20. Insights into $Q^2 \\bar{Q}^2$ states from an effective perspective

    CERN Document Server

    Ametller, Ll

    2015-01-01

    We discuss the two photon coupling of the lightest scalar meson on the basis of an extension of $\\chi$PT. Using low energy data on the pion form-factor and the $\\gamma\\gamma\\to \\pi^+\\pi^-(\\pi^0\\pi^0)$ cross-sections as inputs, we find $\\Gamma(\\sigma\\to\\gamma\\gamma) \\cong 0.126~\\rm{keV} $. The smallness of the result and the relative weight between its components, ${\\Gamma_{\\gamma\\gamma\\to S_1}\\over \\Gamma{ \\gamma\\gamma\\to\\pi\\pi\\to S_1}} < 1$, suggests that the scalar $0^{++}$ meson is mainly a $Q^2\\bar{Q}^2$ state.

  1. An insight into the biophysical characterization of different states of cefotaxime hydrolyzing β-lactamase 15 (CTX-M-15).

    Science.gov (United States)

    Rehman, Md Tabish; Faheem, Mohd; Khan, Asad U

    2015-01-01

    Cefotaxime hydrolyzing β-lactamase-15 (CTX-M-15) is encoded by blaCTX-M-15 gene present on plasmid of various Gram-negative bacteria, such as E. coli, E. cloacae, K. pneumoniae, etc. The widespread dissemination of CTX-M-15 harboring bacteria in hospital as well as community settings is a universal threat as they are resistant to various clinically significant antibiotics. In order to gain an insight into the folding mechanism of CTX-M-15, we carried out pH-induced denaturation study by monitoring Trp fluorescence, far-UV circular dichroism (CD), and ANS fluorescence. We found that the pH-induced denaturation of CTX-M-15 was a three-step process with the accumulation of two stable folding intermediates (XI at pH 2.5 and XII at pH 1.5) in the folding pathway. The intermediates were further characterized by far-UV and near-UV CD analysis, Trp fluorescence, ANS fluorescence, three-dimensional fluorescence, acrylamide quenching, dynamic light scattering, and thermal denaturation studies. We found that XI state lacked tertiary structure but retained most of the secondary structure, its Trp residues were partially exposed to the solvent and its hydrophobic patches were highly accessible to ANS. On the other hand, a complete disruption of tertiary structure along with more than 50% loss in secondary structure was observed in XII state. We conclude that the XI state of CTX-M-15 at pH 2.5 had all the characteristics of a molten globule (MG) state, while its XII state at pH 1.5 was more similar to pre-molten globule (PMG) state. ANS fluorescence also showed that the binding of ANS in XII state was lower than that in the XI state. We propose that the accumulation of MG- and PMG-states was due to separation (at pH 2.5) and then unfolding (at pH 1.5) of the αβα-fold of CTX-M-15, respectively.

  2. Social Media Activism and State Censorship

    NARCIS (Netherlands)

    T. Poell

    2015-01-01

    This chapter interrogates how activist social media communication in authoritarian contexts is shaped through the mutual articulation of social media user practices, business models, and technological architectures, as well as through the controlling efforts of states. It specifically focuses on soc

  3. On the dynamical state of galaxy clusters: insights from cosmological simulations II.

    Science.gov (United States)

    Cui, Weiguang; Power, Chris; Borgani, Stefano; Knebe, Alexander; Lewis, Geraint F.; Murante, Giuseppe; Poole, Gregory B.

    2016-10-01

    Using a suite of cosmology simulations of a sample of >120 galaxy clusters with log (MDM, vir) ≤ 14.5. We compare clusters that form in purely dark matter run and their counterparts in hydro runs and investigate 4 independent parameters, that are normally used to classify dynamical state. We find that the virial ratio η in hydro-dynamical runs is ˜10 per cent lower than in the DM run, and there is no clear separation between the relaxed and unrelaxed clusters for any parameter. Further, using the velocity dispersion deviation parameter ζ, which is defined as the ratio between cluster velocity dispersion σ and the theoretical prediction σ _t = √{G M_{total}/R}, we find that there is a linear correlation between the virial ratio η and this ζ parameter. We propose to use this ζ parameter, which can be easily derived from observed galaxy clusters, as a substitute of the η parameter to quantify the cluster dynamical state.

  4. The dynamical state of the galaxy cluster: Theoretical insights from cosmological simulations

    CERN Document Server

    Cui, Weiguang; Borgani, Stefano; Knebe, Alexander; Lewis, Geraint F; Murante, Giuseppe; Poole, Greg B

    2016-01-01

    Following the work of Cui et al. (2016b, hereafter Paper I), we investigate the dynamical state of the galaxy clusters from the theoretical point of view. After extending to vrial radius $R_{vir}$, we reselect out 123 clusters with $\\log(M_{DM, vir}) \\le 14.5$ from the galaxy cluster samples in Paper I, here DM indicate the dark-matter-only run. These clusters from the two hydro-dynamical runs are matched to the dark-matter-only run using the unique dark matter particle ID. We investigate 4 independent parameters, which are normally used to classify the cluster dynamical state. We find that the virial ratio $\\eta$ from both hydro-dynamical runs is $\\sim$ 10 per cent lower than from the dark-matter-only run; there is no clear bimodal distribution between the relaxed and un-relaxed clusters for all investigated parameters. Further, using the velocity dispersion deviation parameter $\\zeta$ , which is defined as the ratio between cluster velocity dispersion $\\sigma$ and the theoretical prediction $\\sigma_t = \\sqr...

  5. Insight into temperature dependence of GTPase activity in human guanylate binding protein-1.

    Directory of Open Access Journals (Sweden)

    Anjana Rani

    Full Text Available Interferon-γ induced human guanylate binding protein-1(hGBP1 belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1.

  6. Excited state dynamics of thiophene and bithiophene: new insights into theoretically challenging systems.

    Science.gov (United States)

    Prlj, Antonio; Curchod, Basile F E; Corminboeuf, Clémence

    2015-06-14

    The computational elucidation and proper description of the ultrafast deactivation mechanisms of simple organic electronic units, such as thiophene and its oligomers, is as challenging as it is contentious. A comprehensive excited state dynamics analysis of these systems utilizing reliable electronic structure approaches is currently lacking, with earlier pictures of the photochemistry of these systems being conceived based upon high-level static computations or lower level dynamic trajectories. Here a detailed surface hopping molecular dynamics of thiophene and bithiophene using the algebraic diagrammatic construction to second order (ADC(2)) method is presented. Our findings illustrate that ring puckering plays an important role in thiophene photochemistry and that the photostability increases when going upon dimerization into bithiophene.

  7. First insights into the genetic diversity of Mycobacterium tuberculosis strains in Salvador, Bahia State, Brazil

    Directory of Open Access Journals (Sweden)

    Aída Cristina do Nascimento Silva

    2011-09-01

    Full Text Available This study constitutes a first attempt to describe the genetic population structure of Mycobacterium tuberculosis circulating in Salvador, Bahia State, Brazil. A total of 56 confirmed cases of pulmonary tuberculosis, identified between March and June 2008, were analyzed using restriction fragment length polymorphism (IS6110-RFLP. The study population was characterized by a predominance of males (71.43% over 30 years of age (68.75%. Forty-one isolates were found to belong to a single pattern (73.2%, while 15 (26.7% were found in group patterns, forming six clusters. The higher level of diversity observed is much more suggestive of endogenous reactivation than recent transmission.

  8. The Impact of Seawater Saturation State on Early Skeletal Development in Larval Corals: Insights into Scleractinian Biomineralization

    Science.gov (United States)

    Cohen, A. L.; McCorkle, D. C.; de Putron, S.

    2007-12-01

    Understanding the response of coral calcification to changes in seawater saturation state (ocean acidification) could provide important insights into the fundamental processes of scleractinian biomineralization. In particular, larval calcification, which involves initiation of skeletogenesis by a previously non-calcifying planktonic planula, offers a unique opportunity to examine the role and limitations of biological control over an essentially physicochemical process. Larvae of the brooding Atlantic coral Favia fragum were settled in unmodified seawater onto clay tiles within 12h of spawning, and placed into non-through flow 30 L aquaria prior to initiation of calcification. Seawater chemistry was pre-adjusted via HCl addition and continuous bubbling with laboratory air, yielding four aragonite saturation states: Omega(aragonite) = 3.71 (unmodified), 2.4, 1.04, and 0.22. The aquaria were held at 25 °C on a 12h/12h light/dark cycle, and sets of tiles harvested at 1, 5 and 8 days post-spawning. Accretion of aragonite (confirmed by Raman spectroscopy) in all treatments indicates that the settled larvae were able to elevate the saturation state of aquarium seawater sequestered within their calcifying space. However, external aqueous carbonate chemistry had a striking effect on larval mortality, on the nature and timing of basal plate formation, on skeletal growth rates (based on the length and cross-sectional area of septa), and on the structure and organization of aragonite crystals within the septa (imaged using SEM). Larval survival rates at the two lower saturation states was only 40% of that in the control and Omega = 2.35 treatments, and skeletal growth decreased by 30 % (relative to the control) in seawater with saturation state comparable to that predicted for the mid-latitude surface ocean by 2100 AD. SEM imaging of the larval skeletons revealed significant differences in the morphology of aragonite crystals accreted under different conditions. In stark

  9. Functional insights into modulation of BKCa channel activity to alter myometrial contractility

    Directory of Open Access Journals (Sweden)

    Ramón A Lorca

    2014-07-01

    Full Text Available The large-conductance voltage- and Ca2+-activated K+ channel (BKCa is an important regulator of membrane excitability in a wide variety of cells and tissues. In myometrial smooth muscle, activation of BKCa plays essential roles in buffering contractility to maintain uterine quiescence during pregnancy and in the transition to a more contractile state at the onset of labor. Multiple mechanisms of modulation have been described to alter BKCa channel activity, expression, and cellular localization. In the myometrium, BKCa is regulated by alternative splicing, protein targeting to the plasma membrane, compartmentation in membrane microdomains, and posttranslational modifications. In addition, interaction with auxiliary proteins (i.e., β1- and β2-subunits, association with G-protein coupled receptor signaling pathways, such as those activated by adrenergic and oxytocin receptors, and hormonal regulation provide further mechanisms of variable modulation of BKCa channel function in myometrial smooth muscle. Here, we provide an overview of these mechanisms of BKCa channel modulation and provide a context for them in relation to myometrial function.

  10. Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation.

    Science.gov (United States)

    Aguirre, Jacob D; Dunkerley, Karen M; Mercier, Pascal; Shaw, Gary S

    2017-01-10

    Mutations in PARK2 and PARK6 genes are responsible for the majority of hereditary Parkinson's disease cases. These genes encode the E3 ubiquitin ligase parkin and the protein kinase PTEN-induced kinase 1 (PINK1), respectively. Together, parkin and PINK1 regulate the mitophagy pathway, which recycles damaged mitochondria following oxidative stress. Native parkin is inactive and exists in an autoinhibited state mediated by its ubiquitin-like (UBL) domain. PINK1 phosphorylation of serine 65 in parkin's UBL and serine 65 of ubiquitin fully activate ubiquitin ligase activity; however, a structural rationale for these observations is not clear. Here, we report the structure of the phosphorylated UBL domain from parkin. We find that destabilization of the UBL results from rearrangements to hydrophobic core packing that modify its structure. Altered surface electrostatics from the phosphoserine group disrupt its intramolecular association, resulting in poorer autoinhibition in phosphorylated parkin. Further, we show that phosphorylation of both the UBL domain and ubiquitin are required to activate parkin by releasing the UBL domain, forming an extended structure needed to facilitate E2-ubiquitin binding. Together, the results underscore the importance of parkin activation by the PINK1 phosphorylation signal and provide a structural picture of the unraveling of parkin's ubiquitin ligase potential.

  11. Metastability of the Nonlinear Wave Equation: Insights from Transition State Theory

    Science.gov (United States)

    Newhall, Katherine A.; Vanden-Eijnden, Eric

    2017-01-01

    This paper is concerned with the longtime dynamics of the nonlinear wave equation in one-space dimension, u_{tt} - κ^2 u_{xx} +V'(u) =0 quad xin [0,1] where κ >0 is a parameter and V(u) is a potential bounded from below and growing at least like u^2 as |u|→ ∞. Infinite energy solutions of this equation preserve a natural Gibbsian invariant measure, and when the potential is double-welled, for example when V(u) = 1/4 (1-u^2)^2 , there is a regime such that two small disjoint sets in the system's phase-space concentrate most of the mass of this measure. This suggests that the solutions to the nonlinear wave equation can be metastable over these sets, in the sense that they spend long periods of time in these sets and only rarely transition between them. Here, we quantify this phenomenon by calculating exactly via transition state theory (TST) the mean frequency at which the solutions of the nonlinear wave equation with initial conditions drawn from its invariant measure cross a dividing surface lying in between the metastable sets. We also investigate numerically how the mean TST frequency compares to the rate at which a typical solution crosses this dividing surface. These numerical results suggest that the dynamics of the nonlinear wave equation is ergodic and rapidly mixing with respect to the Gibbs invariant measure when the parameter κ in small enough. In this case, successive transitions between the two regions are roughly uncorrelated and their dynamics can be coarse-grained to jumps in a two-state Markov chain whose rate can be deduced from the mean TST frequency. This is a regime in which the dynamics of the nonlinear wave equation displays a metastable behavior that is not fundamentally different from that observed in its stochastic counterpart in which random noise and damping terms are added to the equation. For larger κ, however, the dynamics either stops being ergodic, or its mixing time becomes larger than the inverse of the TST frequency

  12. Franciscana strandings on the north coast of Santa Catarina State and insights into birth period

    Directory of Open Access Journals (Sweden)

    Renan Lopes Paitach

    2013-11-01

    Full Text Available Franciscana, Pontoporia blainvillei, is the most threatened small cetacean in the South Atlantic. Accidental captures in fishing nets is the main problem for this species throughout its distribution. Dead franciscanas found along the coast are an important source of information. This work aimed to analyze the records of dead franciscanas found on the northern coast of Santa Catarina, including Babitonga Bay. Between January 2001 and November 2012, 54 franciscana carcasses were recorded, with the highest number (8 individuals in 2011. Fifty-two percent (n=28 of the carcasses were recorded between August and October. Taking into account that this information was not obtained from a systematic effort, it was not possible to consider this as an estimation of mortality. The largest animal was a female, with a total length of 142 cm. Ten recovered animals (18.5% were smaller than 80 cm, and were considered fetuses or calves. These records indicate that the main birthing period for franciscanas in Santa Catarina is between October and January. The findings presented here contribute to our knowledge of franciscana ecology in the state of Santa Catarina.

  13. Eldercare in the transnational setting: insights from Bangladeshi transnational families in the United States.

    Science.gov (United States)

    Amin, Iftekhar; Ingman, Stan

    2014-09-01

    Little is known about the emotional impact of caregiving for elderly parents on migrant child in the transnational setting. To address this gap in the literature, this study examines the stressors, mediators, and outcomes of eldercare in the transnational context. Data were collected from 21 Bangladeshi immigrant men and women living in the United States who had living parents in Bangladesh over 60 years old. Despite the geographic distance, the migrants provide care to their parents such as emotional support, financial assistance, and arranging for care. While the health status of the care recipients contributed to primary objective stressors, none of the transnational caregivers' narratives reflected the presence of any subjective stressors such as role overload, role captivity, and relational deprivation. Distance and depending on others for hands-on caregiving resulted in feelings of loss of control over the caregiving process. Caregivers experienced a range of emotions from guilt, excessive worrying, and distress over the unpredictability and uncertainty of their circumstances. Kin networks, communicative technologies, and a cultural norm of filial piety contributed to mediating stress. The findings underscore the importance of supportive institutional policies such as visa and travel policies, employment leave, and counseling services for caregivers who provide care for their elderly parents transnationally.

  14. State opportunities for action: Update of states' combined heat and power activities

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Elizabeth [American Council for an Energy-Efficient Economy, Washington, D.C. (United States); Elliott, R. Neal [American Council for an Energy-Efficient Economy, Washington, D.C. (United States)

    2003-10-01

    This report updates the review of state policies with regard to CHP that the American Council for and Energy Efficient Economy completed in 2002. It describes the current activities of states with programs during the initial survey and also reviews new programs offered by the states.

  15. Recent insights into the biological activities and drug delivery systems of tanshinones

    Directory of Open Access Journals (Sweden)

    Cai Y

    2016-01-01

    Full Text Available Yuee Cai,1,* Wenji Zhang,2,* Zirong Chen,3 Zhi Shi,1,2 Chengwei He,1 Meiwan Chen1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 2Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: Tanshinones, the major lipid-soluble pharmacological constituents of the Chinese medicinal herb Tanshen (Salvia miltiorrhiza, have attracted growing scientific attention because of the prospective biomedical applications of these compounds. Numerous pharmacological activities, including anti-inflammatory, anticancer, and cardio-cerebrovascular protection activities, are exhibited by the three primary bioactive constituents among the tanshinones, ie, tanshinone I (TNI, tanshinone IIA (TNIIA, and cryptotanshinone (CPT. However, due to their poor solubility and low dissolution rate, the clinical applications of TNI, TNIIA, and CPT are limited. To solve these problems, many studies have focused on loading tanshinones into liposomes, nanoparticles, microemulsions, cyclodextrin inclusions, solid dispersions, and so on. In this review, we aim to offer an updated summary of the biological activities and drug delivery systems of tanshinones to provide a reference for these constituents in clinical applications. Keywords: tanshinones, biological activities, drug delivery systems, bioavailability, solubility

  16. Stimulating Investment Development through Transformation of State Banks Activity

    Directory of Open Access Journals (Sweden)

    Kulpinska Lidiya K.

    2013-12-01

    Full Text Available The article considers significance of state corporations and state financial institutions in stimulation of investments into the fixed capital of the country and considers problems of increase of efficiency of activity of these institutions in the world and Ukraine. It considers the state sector of the developing countries through the prism of activity of state financial and non-financial corporations. It analyses theories of positive and negative features of carrying out state investing through state-owned banks. It analyses the role of state financial corporations in Ukraine, in particular, in crediting and expansion of the portfolio of acquired governmental bonds and offers ways of its increase in the context of necessity of directing funds into investment development.

  17. Active Learning of Nondeterministic Finite State Machines

    Directory of Open Access Journals (Sweden)

    Warawoot Pacharoen

    2013-01-01

    Full Text Available We consider the problem of learning nondeterministic finite state machines (NFSMs from systems where their internal structures are implicit and nondeterministic. Recently, an algorithm for inferring observable NFSMs (ONFSMs, which are the potentially learnable subclass of NFSMs, has been proposed based on the hypothesis that the complete testing assumption is satisfied. According to this assumption, with an input sequence (query, the complete set of all possible output sequences is given by the so-called Teacher, so the number of times for asking the same query is not taken into account in the algorithm. In this paper, we propose LNM*, a refined ONFSM learning algorithm that considers the amount for repeating the same query as one parameter. Unlike the previous work, our approach does not require all possible output sequences in one answer. Instead, it tries to observe the possible output sequences by asking the same query many times to the Teacher. We have proved that LNM* can infer the corresponding ONFSMs of the unknown systems when the number of tries for the same query is adequate to guarantee the complete testing assumption. Moreover, the proof shows that our algorithm will eventually terminate no matter whether the assumption is fulfilled or not. We also present the theoretical time complexity analysis of LNM*. In addition, experimental results demonstrate the practical efficiency of our approach.

  18. Metaproteomics of our microbiome - Developing insight in function and activity in man and model systems

    NARCIS (Netherlands)

    Kolmeder, C.; Vos, de W.M.

    2014-01-01

    We are all colonized by a large microbiome, a complex set of microbes that have intimate associations with us. Culture-based approaches have provided insights in the complexity of the microbial communities living on surfaces inside and outside the body. However, the application of high-throughput se

  19. CMS Grid Activities in the United States

    Institute of Scientific and Technical Information of China (English)

    I.Fisk; J.Amundson; 等

    2001-01-01

    The CMS groups in the USA are actively involved in several grid-elated projects,including the DoE-funded Particle Physics Data Grid(PPDG)and the NSFfunded Grid Physics Network(GriPhyN).We present developments of :the Grid data Management Pilot (GDMP) software;a Java Analysis Studio-based prototype remote analysis service for CMS data;tools for automating job submission schemes for large scale distributed simulation and reconstruction runs for CMS;modeling and development of job scheduling schemes using the MONARC toolkit;a robust execution service for distributed processors.The deployment and use of these tools at prototype Tier1 and Tier2 computing centers in the USA is described.

  20. Some insights about the activity of the Ceboruco Volcano (Nayarit, Mexico) from recent seismic low-frequency activity

    Science.gov (United States)

    Rodríguez Uribe, María Carolina; Núñez-Cornú, Francisco Javier; Nava Pichardo, Fidencio Alejandro; Suárez-Plascencia, Carlos

    2013-10-01

    The Ceboruco stratovolcano (2,280 m.a.s.l.) is located in Nayarit, Mexico, at the western end of the Mexican volcanic belt, near several population centers and by the side of a strategic highway. During the last 1,000 years it has had, on the average, one eruption every 125 years. It last eruptive activity began in 1870, and during the following 5 years it presented superficial activity including vapor emissions, ash falls, and rhyodacitic lava flows along the southeast side. A data set consisting of 139 low-frequency volcanic-type earthquakes, recorded from March 2003 to July 2008 at the CEBN triaxial short period digital station on the southwestern side of the volcano, was classified according to waveform and spectral characteristics into four families: short duration, extended coda, bobbin, and modulated amplitude. Approximate hypocentral locations indicate that there is no particular location for events of any family, but rather that all events occur at different points within the volcano. The presence of ongoing volcanic-earthquake activity together with the ongoing vapor emissions indicate that the Ceboruco volcano continues to be active, and the higher occurrence rates of short-duration events, as compared with those for the other families, could indicate an increase in the stress in the volcanic edifice. This apparent stress increase, together with the fact that the last eruption occurred 143 years ago, tell us that the Ceboruco may be approaching a critical state, and may represent a hazard to the surrounding communities and economic activities.

  1. Energy metabolism in Mycobacterium gilvum PYR-GCK: insights from transcript expression analyses following two states of induction.

    Directory of Open Access Journals (Sweden)

    Abimbola Comfort Badejo

    Full Text Available Mycobacterium gilvum PYR-GCK, a pyrene degrading bacterium, has been the subject of functional studies aimed at elucidating mechanisms related to its outstanding pollutant bioremediation/biodegradation activities. Several studies have investigated energy production and conservation in Mycobacterium, however, they all focused on the pathogenic strains using their various hosts as induction sources. To gain greater insight into Mycobacterium energy metabolism, mRNA expression studies focused on respiratory functions were performed under two different conditions using the toxic pollutant pyrene as a test substrate and glucose as a control substrate. This was done using two transcriptomic techniques: global transcriptomic RNA-sequencing and quantitative Real-Time PCR. Growth in the presence of pyrene resulted in upregulated expression of genes associated with limited oxygen or anaerobiosis in M. gilvum PYR-GCK. Upregulated genes included succinate dehydrogenases, nitrite reductase and various electron donors including formate dehydrogenases, fumarate reductases and NADH dehydrogenases. Oxidative phosphorylation genes (with respiratory chain complexes I, III -V were expressed at low levels compared to the genes coding for the second molecular complex in the bacterial respiratory chain (fumarate reductase; which is highly functional during microaerophilic or anaerobic bacterial growth. This study reveals a molecular adaptation to a hypoxic mode of respiration during aerobic pyrene degradation. This is likely the result of a cellular oxygen shortage resulting from exhaustion of the oxygenase enzymes required for these degradation activities in M. gilvum PYR-GCK.

  2. Monitoring Affect States during Effortful Problem Solving Activities

    Science.gov (United States)

    D'Mello, Sidney K.; Lehman, Blair; Person, Natalie

    2010-01-01

    We explored the affective states that students experienced during effortful problem solving activities. We conducted a study where 41 students solved difficult analytical reasoning problems from the Law School Admission Test. Students viewed videos of their faces and screen captures and judged their emotions from a set of 14 states (basic…

  3. 34 CFR 300.812 - Reservation for State activities.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Reservation for State activities. 300.812 Section 300.812 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION...

  4. 34 CFR 300.814 - Other State-level activities.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Other State-level activities. 300.814 Section 300.814 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION...

  5. Computational characterisation of the interactions between human ST6Gal I and transition-state analogue inhibitors: insights for inhibitor design.

    Science.gov (United States)

    Montgomery, Andrew; Szabo, Rémi; Skropeta, Danielle; Yu, Haibo

    2016-05-01

    Human β-galactoside α-2,6-sialyltransferase I (hST6Gal I) catalyses the synthesis of sialylated glycoconjugates involved in cell-cell interactions. Overexpression of hST6Gal I is observed in many different types of cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase (ST) inhibitors have been developed based on the natural donor, cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac). Of these, analogues that are structurally similar to the transition state exhibit the highest inhibitory activity. In order to design inhibitors that are readily accessible synthetically and with favourable pharmacokinetic properties, an investigation of the replacement of the charged phosphodiester-linker, present in many ST inhibitors, with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been undertaken. To investigate this, molecular docking and molecular dynamics simulations were performed. These simulations provided an insight into the binding mode of previously reported phosphodiester-linked ST inhibitors and demonstrated that targeting the proposed sialyl acceptor site is a viable option for producing selective inhibitors. The potential for a carbamate- or triazole-linker as an isosteric replacement for the phosphodiester in transition-state analogue ST inhibitors was established using molecular docking. Molecular dynamics simulations of carbamate- and phosphodiester-linked compounds revealed that both classes exhibit consistent interactions with hST6Gal I. Overall, the results obtained from this study provide a rationale for synthetic and biological evaluation of triazole- and carbamate-linked transition-state analogue ST inhibitors as potential new antimetastatic agents.

  6. Insights into the electrochemical activity of nanosized {alpha}-LiFeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Morales, J.; Santos-Pena, J.; Trocoli, R. [Departamento de Quimica Inorganica e Ingenieria Quimica, Edificio Marie Curie, Campus de Rabanales, Universidad de Cordoba, Cordoba 14071 (Spain); Franger, S. [Laboratoire de Physico-Chimie de l' Etat Solide, ICMMO, Universite Paris XI, Orsay 91405 (France); Rodriguez-Castellon, E. [Departamento de Quimica Inorganica, Cristalografia y Mineralogia, Campus de Teatinos, Universidad de Malaga, Malaga 29071 (Spain)

    2008-09-20

    In recent work [J. Morales, J. Santos-Pena, Electrochem. Commun. 9 (2007) 2116], we prepared nanosized {alpha}-LiFeO{sub 2} with increased electrochemical activity in lithium cells relative to various lithium ferrite polymorphs. In this work, we studied the previous electrodes in different charge states in order to obtain a more accurate picture of the phenomena occurring during cycling. Exsitu X-ray photoelectron spectroscopy (XPS) measurements confirmed the oxidation/reduction of iron atoms during the charge/discharge process. The electrochemical impedance spectroscopy results suggested that the electrolyte is not oxidised during the first charge, but rather than a solid electrolyte interface is formed after one cycle. Also, thermal tests revealed that Fe(IV) present in the electrodes reacted with the electrolyte to form oxidised carbon species. Finally, {alpha}-LiFeO{sub 2} was tested as a positive electrode material in a lithium battery under different regimes. Stabilised capacities up to 150 mAh g{sup -1} were obtained under a C/4 regime. This lithium ferrite is therefore an attractive alternative to LiCoO{sub 2}. (author)

  7. On the way of classifying new states of active matter

    Science.gov (United States)

    Menzel, Andreas M.

    2016-07-01

    With ongoing research into the collective behavior of self-propelled particles, new states of active matter are revealed. Some of them are entirely based on the non-equilibrium character and do not have an immediate equilibrium counterpart. In their recent work, Romanczuk et al (2016 New J. Phys. 18 063015) concentrate on the characterization of smectic-like states of active matter. A new type, referred to by the authors as smectic P, is described. In this state, the active particles form stacked layers and self-propel along them. Identifying and classifying states and phases of non-equilibrium matter, including the transitions between them, is an up-to-date effort that will certainly extend for a longer period into the future.

  8. New insights into prevention of disability by physical activity and exercise

    NARCIS (Netherlands)

    Tak, E.; Dronkers, J.; Koeneman, M.; Hopman-Rock, M.

    2012-01-01

    Abstract for the International Society for Aging and Physical activity's 8th World Congress on Aging and Physical Activity: A celebration of Diversity and Inclusion in Active Ageing, August 13-17 2012.

  9. Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Munoz-Munoz, Jose Luis [GENZ - Grupo de Investigacion Enzimologia, Departamento de Bioquimica y Biologia Molecular-A, Facultad de Biologia, Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia, E-30100 Espinardo, Murcia (Spain); Berna, Jose [Grupo de Quimica Organica Sintetica, Departamento de Quimica Organica, Facultad de Quimica Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia (Spain); Garcia-Molina, Maria del Mar; Garcia-Molina, Francisco [GENZ - Grupo de Investigacion Enzimologia, Departamento de Bioquimica y Biologia Molecular-A, Facultad de Biologia, Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia, E-30100 Espinardo, Murcia (Spain); Garcia-Ruiz, Pedro Antonio [QCPAI - Grupo de Quimica de Carbohidratos, Polimeros y Aditivos Industriales, Departamento de Quimica Organica, Facultad de Quimica Campus Internacional de Excelencia Campus Mare Nostrum, Universidad de Murcia (Spain); Varon, Ramon [Departamento de Quimica-Fisica, Escuela de Ingenieros Industriales de Albacete, Universidad de Castilla la Mancha, Avda. Espana s/n. Campus Universitario, E-02071 Albacete (Spain); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer The action the copper complexes and tyrosinase on phenols is equivalent. Black-Right-Pointing-Pointer Isotope effect showed that nucleophilic attack to copper atom may be the slower step. Black-Right-Pointing-Pointer The value of {rho} (Hammett constant) supports an electrophilic aromatic substitution. Black-Right-Pointing-Pointer Data obtained in steady state pH 7 conditions support the mechanism of Scheme 1SM. -- Abstract: A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: k{sub cat}{sup m} and the Michaelis constant, K{sub M}{sup m}. Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group ({delta}) and {sigma}{sub p}{sup +}, enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form E{sub ox} (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant {rho} of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of k{sub cat}{sup f{sub n}}/k{sub cat}{sup f{sub 0}} against n (atom fractions of deuterium), where k{sub cat}{sup f{sub n}} is the catalytic constant for a molar fraction of deuterium (n) and k{sub cat}{sup f{sub 0}} is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that

  10. Translation-rotation states of H2 in C60: New insights from a perturbation-theory treatment

    Science.gov (United States)

    Felker, Peter M.; Bačić, Zlatko

    2016-08-01

    We report an investigation of the translation-rotation (TR) level structure of H2 entrapped in C60, in the rigid-monomer approximation, by means of a low-order perturbation theory (PT). We focus in particular on the degree to which PT can accurately account for that level structure, by comparison with the variational quantum five-dimensional calculations. To apply PT to the system, the interaction potential of H2@C60 is decomposed into a sum over bipolar spherical tensors. A zeroth-order Hamiltonian, Hˆ 0, is then constructed as the sum of the TR kinetic-energy operator and the one term in the tensor decomposition of the potential that depends solely on the radial displacement of the H2 center of mass (c.m.) from the cage center. The remaining terms in the potential are treated as perturbations. The eigenstates of Hˆ 0, constructed to also account for the coupling of the angular momentum of the H2 c.m. about the cage center with the rotational angular momentum of the H2 about the c.m., are taken as the PT zeroth-order states. This zeroth-order level structure is shown to be an excellent approximation to the true one except for two types of TR-level splittings present in the latter. We then show that first-order PT accounts very well for these splittings, with respect to both their patterns and magnitudes. This allows one to connect specific features of the level structure with specific features of the potential-energy surface, and provides important new physical insight into the characteristics of the TR level structure.

  11. Mild activation of CeO2-supported gold nanoclusters and insight into the catalytic behavior in CO oxidation.

    Science.gov (United States)

    Li, Weili; Ge, Qingjie; Ma, Xiangang; Chen, Yuxiang; Zhu, Manzhou; Xu, Hengyong; Jin, Rongchao

    2016-01-28

    We report a new activation method and insight into the catalytic behavior of a CeO2-supported, atomically precise Au144(SR)60 nanocluster catalyst (where thiolate -SR = -SCH2CH2Ph) for CO oxidation. An important finding is that the activation of the catalyst is closely related to the production of active oxygen species on CeO2, rather than ligand removal of the Au144(SR)60 clusters. A mild O2 pretreatment (at 80 °C) can activate the catalyst, and the addition of reductive gases (CO or H2) can enhance the activation effects of O2 pretreatment via a redox cycle in which CO could reduce the surface of CeO2 to produce oxygen vacancies-which then adsorb and activate O2 to produce more active oxygen species. The CO/O2 pulse experiments confirm that CO is adsorbed on the cluster catalyst even with ligands on, and active oxygen species present on the surface of the pretreated catalyst reacts with CO pulses to generate CO2. The Au144(SR)60/CeO2 exhibits high CO oxidation activity at 80 °C without the removal of thiolate ligands. The surface lattice-oxygen of the support CeO2 possibly participates in the oxidation of CO over the Au144(SR)60/CeO2 catalyst.

  12. Confrontation Between Judicial Activism and State of Exception

    Directory of Open Access Journals (Sweden)

    Alexandre Pedro Moura D’Almeida

    2017-01-01

    Full Text Available The judiciary has excelled in the international and national scene, reaching role of great importance, thus creating opposition to the legislative and executive powers. The center of gravity of the sovereign power of the state moves toward the judiciary, that happens to have a more active role and controlling of the others powers, but also appears as a great defender of social and fundamental rights causes, seeking to make an effective constitution. Its great public notoriety has attracted great distrust of various sectors of society, especially by the two powers that have an increasing interference. Arises, therefore, a speech that the judiciary would be reversing into a big and uncontrollable power, increasing the suspicion that now it would be living in a real dictatorship of the judiciary through judicial activism. There is a growing concern with the expansion of activism and the role of the judiciary. The purpose of this work is to conceptualize and approach the judicial activism and the state of exception to search and reveal if there is any similarity, to then draw up a possible answer to the concern of forming a dictatorship of the judiciary. The state of exception is one of the rule of law paradoxes, while activism is a political manifestation of the judiciary. The similarity between the institutes appears as appalling in a dynamic expansion of political power of a state institution exercising judicial function, putting in check who would be the sovereign in a rule of law and democratic state.

  13. Resting state brain activity and functional brain mapping

    Institute of Scientific and Technical Information of China (English)

    Zhao Xiaohu; Wang Peijun; Tang Xiaowei

    2007-01-01

    Functional brain imaging studies commonly use either resting or passive task states as their control conditions, and typically identify the activation brain region associated with a specific task by subtracting the resting from the active task conditions. Numerous studies now suggest, however, that the resting state may not reflect true mental "rest" conditions. The mental activity that occurs during"rest" might therefore greatly influence the functional neuroimaging observations that are collected through the usual subtracting analysis strategies. Exploring the ongoing mental processes that occur during resting conditions is thus of particular importance for deciphering functional brain mapping results and obtaining a more comprehensive understanding of human brain functions. In this review article, we will mainly focus on the discussion of the current research background of functional brain mapping at resting state and the physiological significance of the available neuroimaging data.

  14. Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.

    Directory of Open Access Journals (Sweden)

    Basavaraju G Sanganahalli

    Full Text Available Mitochondrial Ca(2+ uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca(2+ uptake capacities on intrinsic brain activity using clinically relevant markers. From a multi-compartment estimate of probable baseline Ca(2+ ranges in the brain, we hypothesized that reduced or enhanced mitochondrial Ca(2+ uptake capacity would decrease or increase spontaneous neuronal activity respectively. As resting state fMRI-BOLD fluctuations and stimulus-evoked BOLD responses have similar physiological origins [1] and stimulus-evoked neuronal and hemodynamic responses are modulated by mitochondrial Ca(2+ uptake capacity [2], [3] respectively, we tested our hypothesis by measuring hemodynamic fluctuations and spontaneous neuronal activities during normal and altered mitochondrial functional states. Mitochondrial Ca(2+ uptake capacity was perturbed by pharmacologically inhibiting or enhancing the mitochondrial Ca(2+ uniporter (mCU activity. Neuronal electrical activity and cerebral blood flow (CBF fluctuations were measured simultaneously and integrated with fMRI-BOLD fluctuations at 11.7T. mCU inhibition reduced spontaneous neuronal activity and the resting state functional connectivity (RSFC, whereas mCU enhancement increased spontaneous neuronal activity but reduced RSFC. We conclude that increased or decreased mitochondrial Ca(2+ uptake capacities lead to diminished resting state modes of brain functional connectivity.

  15. Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity

    Science.gov (United States)

    Watanabe, Jun-ichiro; Atsumori, Hirokazu; Kiguchi, Masashi

    2016-01-01

    Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID:27199715

  16. Informal face-to-face interaction improves mood state reflected in prefrontal cortex activity

    Directory of Open Access Journals (Sweden)

    Jun-Ichiro eWatanabe

    2016-05-01

    Full Text Available Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS.We also observed that the verbal WM task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC activity accompanied by working memory (WM tasks measured by near-infrared spectroscopy (NIRS.

  17. New insights into the activation mechanism of store-operated calcium channels:roles of STIM and Orai

    Institute of Scientific and Technical Information of China (English)

    Rui-wei GUO; Lan HUANG

    2008-01-01

    The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER)is a ubiquitous signaling mechanism,the molecular basis of which has remained elusive for the past two decades.Store-operated Ca2+-release-activated Ca2+(CRAC)channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement.In a set of breakthrough studies over the past two years,stromal interaction molecule l(STIM1,tbe ER Ca2+ sensor) and Orail(a pore-forming subunit of the CRAC channel)have been identified.Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels(SOCCs).

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

    Science.gov (United States)

    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.

  19. 2-(pyrazin-2-yloxy)acetohydrazide analogs QSAR Study: An insight into the structural basis of antimycobacterial activity.

    Science.gov (United States)

    Gupta, Revathi A; Gupta, Arun K; Soni, Love K; Kaskhedikar, Satish Gopalrao

    2010-11-01

    Quantitative structure activity relationship analysis based on classical Hansch approach was adopted on reported novel series of 2-(pyrazin-2-yloxy)acetohydrazide analogs. Various types of descriptors like topological, spatial, thermodynamic, and electronic were used to derive a quantitative relationship between the antitubercular activity and structural properties. The consensus scoring function showed a significant statistics of training and test set. Coefficient of determination (r²) of consensus model and predictive squared correlation coefficient (r²(pred)) were found to be 0.889 and 0.782, respectively. The model is not only able to predict the activity of test compounds but also explained the important structural features of the molecules in a quantitative manner. The study revealed that antimycobacterium activity is predominantly explained by the molecular connectivity indices of length 6, hydrogen donor feature of the analogs, and shape factors of the substituent. The comparative investigation of antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella typhi provided structural insights on how modulation of the molecular connectivity indices, energy of lowest unoccupied molecular orbital, accessible surface area, and moment of inertia of the analogs could be usefully made to optimize the antibacterial activity.

  20. Transcriptional Activation of Inflammatory Genes: Mechanistic Insight into Selectivity and Diversity.

    Science.gov (United States)

    Ahmed, Afsar U; Williams, Bryan R G; Hannigan, Gregory E

    2015-11-11

    Acute inflammation, an integral part of host defence and immunity, is a highly conserved cellular response to pathogens and other harmful stimuli. An inflammatory stimulation triggers transcriptional activation of selective pro-inflammatory genes that carry out specific functions such as anti-microbial activity or tissue healing. Based on the nature of inflammatory stimuli, an extensive exploitation of selective transcriptional activations of pro-inflammatory genes is performed by the host to ensure a defined inflammatory response. Inflammatory signal transductions are initiated by the recognition of inflammatory stimuli by transmembrane receptors, followed by the transmission of the signals to the nucleus for differential gene activations. The differential transcriptional activation of pro-inflammatory genes is precisely controlled by the selective binding of transcription factors to the promoters of these genes. Among a number of transcription factors identified to date, NF-κB still remains the most prominent and studied factor for its diverse range of selective transcriptional activities. Differential transcriptional activities of NF-κB are dictated by post-translational modifications, specificities in dimer formation, and variability in activation kinetics. Apart from the differential functions of transcription factors, the transcriptional activation of selective pro-inflammatory genes is also governed by chromatin structures, epigenetic markers, and other regulators as the field is continuously expanding.

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

    Science.gov (United States)

    Vieira, F M; Bisch, P M

    1994-01-01

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

  2. Data inconsistencies from states with unconventional oil and gas activity.

    Science.gov (United States)

    Malone, Samantha; Kelso, Matthew; Auch, Ted; Edelstein, Karen; Ferrar, Kyle; Jalbert, Kirk

    2015-01-01

    The quality and availability of unconventional oil and gas (O&G) data in the United States have never been compared methodically state-to-state. By conducting such an assessment, this study seeks to better understand private and publicly sourced data variability and to identify data availability gaps. We developed an exploratory data-grading tool - Data Accessibility and Usability Index (DAUI) - to guide the review of O&G data quality. Between July and October 2013, we requested, collected, and assessed 5 categories of unconventional O&G data (wells drilled, violations, production, waste, and Class II disposal wells) from 10 states with active drilling activity. We based our assessment on eight data quality parameters (accessibility, usability, point location, completeness, metadata, agency responsiveness, accuracy, and cost). Using the DAUI, two authors graded the 10 states and then averaged their scores. The average score received across all states, data categories, and parameters was 67.1 out of 100, largely insufficient for proper data transparency. By state, Pennsylvania received the highest average ( = 93.5) and ranked first in all but one data category. The lowest scoring state was Texas ( = 44) largely due to its policy of charging for certain data. This article discusses the various reasons for scores received, as well as methodological limitations of the assessment metrics. We argue that the significant variability of unconventional O&G data-and its availability to the public-is a barrier to regulatory and industry transparency. The lack of transparency also impacts public education and broader participation in industry governance. This study supports the need to develop a set of data best management practices (BMPs) for state regulatory agencies and the O&G industry, and suggests potential BMPs for this purpose.

  3. Insights into structure and activity of natural compound inhibitors of pneumolysin

    Science.gov (United States)

    Li, Hongen; Zhao, Xiaoran; Deng, Xuming; Wang, Jianfeng; Song, Meng; Niu, Xiaodi; Peng, Liping

    2017-01-01

    Pneumolysin is the one of the major virulence factor of the bacterium Streptococcus pneumoniae. In previous report, it is shown that β-sitosterol, a natural compound without antimicrobial activity, is a potent antagonist of pneumolysin. Here, two new pneumolysin natural compound inhibitors, with differential activity, were discovered via haemolysis assay. To explore the key factor of the conformation for the inhibition activity, the interactions between five natural compound inhibitors with differential activity and pneumolysin were reported using molecular modelling, the potential of mean force profiles. Interestingly, it is found that incorporation of the single bond (C22-C23-C24-C25) to replace the double bond (hydrocarbon sidechain) improved the anti-haemolytic activity. In view of the molecular modelling, binding of the five inhibitors to the conserved loop region (Val372, Leu460, and Tyr461) of the cholesterol binding sites led to stable complex systems, which was consistent with the result of β-sitosterol. Owing to the single bond (C22-C23-C24-C25), campesterol and brassicasterol could form strong interactions with Val372 and show higher anti-haemolytic activity, which indicated that the single bond (C22-C23-C24-C25) in inhibitors was required for the anti-haemolytic activity. Overall, the current molecular modelling work provides a starting point for the development of rational design and higher activity pneumolysin inhibitors. PMID:28165051

  4. Superior Temporal Activation as a Function of Linguistic Knowledge: Insights from Deaf Native Signers Who Speechread

    Science.gov (United States)

    Capek, Cheryl M.; Woll, Bencie; MacSweeney, Mairead; Waters, Dafydd; McGuire, Philip K.; David, Anthony S.; Brammer, Michael J.; Campbell, Ruth

    2010-01-01

    Studies of spoken and signed language processing reliably show involvement of the posterior superior temporal cortex. This region is also reliably activated by observation of meaningless oral and manual actions. In this study we directly compared the extent to which activation in posterior superior temporal cortex is modulated by linguistic…

  5. Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis.

    Science.gov (United States)

    Jeong, Jae-Hee; Cha, Hyung Jin; Ha, Sung-Chul; Rojviriya, Catleya; Kim, Yeon-Gil

    2014-10-03

    EgtD is an S-adenosyl-l-methionine (SAM)-dependent histidine N,N,N-methyltransferase that catalyzes the formation of hercynine from histidine in the ergothioneine biosynthetic process of Mycobacterium smegmatis. Ergothioneine is a secreted antioxidant that protects mycobacterium from oxidative stress. Here, we present three crystal structures of EgtD in the apo form, the histidine-bound form, and the S-adenosyl-l-homocysteine (SAH)/histidine-bound form. The study revealed that EgtD consists of two distinct domains: a typical methyltransferase domain and a unique substrate binding domain. The histidine binding pocket of the substrate binding domain primarily recognizes the imidazole ring and carboxylate group of histidine rather than the amino group, explaining the high selectivity for histidine and/or (mono-, di-) methylated histidine as substrates. In addition, SAM binding to the MTase domain induced a conformational change in EgtD to facilitate the methyl transfer reaction. The structural analysis provides insights into the putative catalytic mechanism of EgtD in a processive trimethylation reaction.

  6. INVESTMENT ACTIVITY OF NON-STATE FOUNDS OF RUSSIA

    Directory of Open Access Journals (Sweden)

    Kobylinsky S. V.

    2016-04-01

    Full Text Available Currently, pension by virtue of their social significance in favor of one of the main socially important guarantee of stable development of society, to ensure the financial and budgetary sphere of the state. Private pension founds are viewed as an instrument to raise the material well-being of pensioners. The social significance of non-state pension funds is to involve the population in the sphere of voluntary pension insurance. The author analyzed the role of non-state pension funds in acting to pension system. The article subjected to a detailed analysis of the norms of a number of Federal laws, fixing the investment activity of non-state pension found. The author concludes that there is a need to improve existing legislation on investment activity of non-state pension found. As well, the authors indicated some legal problems that occur in practice arising from owners of the investment portfolio. The authors have analyzed the performance of pension funds and formed an opinion about the state of the whole system. Following consideration of the practical problems has been offered for both theoretical and practical ways to address them in order to prevent violation

  7. The Current State of Marketing Activity among Higher Education Institutions.

    Science.gov (United States)

    Newman, Cynthia M.

    2002-01-01

    Investigated the current state of marketing, marketing research, and planning practices at four-year higher education institutions. Builds upon previous studies by Blackburn (1979) and Goldgehn (1982 and 1989). Determined whether the use and apparent understanding of marketing and its attendant activities by admissions and enrollment management…

  8. Resting-state beta and gamma activity in Internet addiction.

    Science.gov (United States)

    Choi, Jung-Seok; Park, Su Mi; Lee, Jaewon; Hwang, Jae Yeon; Jung, Hee Yeon; Choi, Sam-Wook; Kim, Dai Jin; Oh, Sohee; Lee, Jun-Young

    2013-09-01

    Internet addiction is the inability to control one's use of the Internet and is related to impulsivity. Although a few studies have examined neurophysiological activity as individuals with Internet addiction engage in cognitive processing, no information on spontaneous EEG activity in the eyes-closed resting-state is available. We investigated resting-state EEG activities in beta and gamma bands and examined their relationships with impulsivity among individuals with Internet addiction and healthy controls. Twenty-one drug-naïve patients with Internet addiction (age: 23.33 ± 3.50 years) and 20 age-, sex-, and IQ-matched healthy controls (age: 22.40 ± 2.33 years) were enrolled in this study. Severity of Internet addiction was identified by the total score on Young's Internet Addiction Test. Impulsivity was measured with the Barratt Impulsiveness Scale-11 and a stop-signal task. Resting-state EEG during eyes closed was recorded, and the absolute/relative power of beta and gamma bands was analyzed. The Internet addiction group showed high impulsivity and impaired inhibitory control. The generalized estimating equation showed that the Internet-addiction group showed lower absolute power on the beta band than did the control group (estimate = -3.370, p Internet addiction as well as with the extent of impulsivity. The present study suggests that resting-state fast-wave brain activity is related to the impulsivity characterizing Internet addiction. These differences may be neurobiological markers for the pathophysiology of Internet addiction.

  9. Steady-state organization of binary mixtures by active impurities

    DEFF Research Database (Denmark)

    Sabra, Mads Christian; Gilhøj, Henriette; Mouritsen, Ole G.

    1998-01-01

    The structural reorganization of a phase-separated binary mixture in the presence of an annealed dilution of active impurities is studied by computer-simulation techniques via a simple two-dimensional lattice-gas model. The impurities, each of which has two internal states with different affinity...

  10. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    Directory of Open Access Journals (Sweden)

    О. Davydova

    2013-11-01

    Full Text Available In the article the existing model of state regulation of the development of tourism. Expediency of the European model of state regulation of tourism development in Ukraine. It is noted that the European model of state regulation of tourism activities based on the coordination of marketing activities and the development of cooperation between the public and private sectors. The basic forms of public-private partnerships and the advantages of using cluster model of development of tourism, namely, contracts, production sharing agreement, lease, joint venture. Promising areas of application of the PPP identified the transport sector, housing and utilities, energy and tourism sector. The features of cluster formations in the country and the prospects for tourism clusters.

  11. Epoxide hydrolase-catalyzed enantioselective conversion of trans-stilbene oxide: Insights into the reaction mechanism from steady-state and pre-steady-state enzyme kinetics.

    Science.gov (United States)

    Archelas, Alain; Zhao, Wei; Faure, Bruno; Iacazio, Gilles; Kotik, Michael

    2016-02-01

    A detailed kinetic study based on steady-state and pre-steady-state measurements is described for the highly enantioselective epoxide hydrolase Kau2. The enzyme, which is a member of the α/β-hydrolase fold family, preferentially reacts with the (S,S)-enantiomer of trans-stilbene oxide (TSO) with an E value of ∼200. The enzyme follows a classical two-step catalytic mechanism with formation of an alkyl-enzyme intermediate in the first step and hydrolysis of this intermediate in a rate-limiting second step. Tryptophan fluorescence quenching during TSO conversion appears to correlate with alkylation of the enzyme. The steady-state data are consistent with (S,S) and (R,R)-TSO being two competing substrates with marked differences in k(cat) and K(M) values. The high enantiopreference of the epoxide hydrolase is best explained by pronounced differences in the second-order alkylation rate constant (k2/K(S)) and the alkyl-enzyme hydrolysis rate k3 between the (S,S) and (R,R)-enantiomers of TSO. Our data suggest that during conversion of (S,S)-TSO the two active site tyrosines, Tyr(157) and Tyr(259), serve mainly as electrophilic catalysts in the alkylation half-reaction, polarizing the oxirane oxygen of the bound epoxide through hydrogen bond formation, however, without fully donating their hydrogens to the forming alkyl-enzyme intermediate.

  12. Mechanistic insights into caspase-9 activation by the structure of the apoptosome holoenzyme

    Science.gov (United States)

    Li, Yini; Zhou, Mengying; Hu, Qi; Bai, Xiao-chen; Huang, Weiyun; Shi, Yigong

    2017-01-01

    Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme. The molecular mechanism of caspase-9 activation remains largely enigmatic. Here, we report the cryoelectron microscopy (cryo-EM) structure of an apoptotic holoenzyme and structure-guided biochemical analyses. The caspase recruitment domains (CARDs) of Apaf-1 and caspase-9 assemble in two different ways: a 4:4 complex docks onto the central hub of the apoptosome, and a 2:1 complex binds the periphery of the central hub. The interface between the CARD complex and the central hub is required for caspase-9 activation within the holoenzyme. Unexpectedly, the CARD of free caspase-9 strongly inhibits its proteolytic activity. These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain. PMID:28143931

  13. New insights into the antioxidant activity and components in crude oat oil and soybean oil.

    Science.gov (United States)

    Chen, Hao; Qiu, Shuang; Gan, Jing; Li, Zaigui; Nirasawa, Satoru; Yin, Lijun

    2016-01-01

    Developing new antioxidants and using natural examples is of current interest. This study evaluated the antioxidant activities and the ability to inhibit soybean oil oxidation of oat oil obtained with different solvents. Oat oil extract obtained by ethanol extraction gave the highest antioxidant activity with a DPPH radical (1,1-diphenyl-2-picrylhydrazyl) scavenging activity of 88.2 % and a reducing power (A 700) of 0.83. Oat oil extracted by ethanol contained the highest polyphenol and α-tocopherol content. Significant correlation was observed between the total polyphenol contents, individual phenolic acid, α-tocopherol, and DPPH radical scavenging activity. Soybean oil with 2 % added oat oil showed low malondialdehyde content (8.35 mmol mL(-1)), suggesting that the added oat oil inhibited oxidation. Oat oil showed good antioxidant activity, especially when extracted with ethanol which could also retard the oxidation of soybean oil . DPPH radical scavenging activity was the best method to evaluate the antioxidant activity and components of oat oil.

  14. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations.

    Science.gov (United States)

    Liu, Shenping; Ammirati, Mark J; Song, Xi; Knafels, John D; Zhang, Jeff; Greasley, Samantha E; Pfefferkorn, Jeffrey A; Qiu, Xiayang

    2012-04-20

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk.

  15. [NiFe] dithiolene diphosphine complex for hydrogen gas activation: a Theoretic Insight

    CERN Document Server

    GuYan, Jing

    2015-01-01

    A diphosphino-nickel-iron dithiolene complex, [Ni(bdt)(dppf)] (bdt = 1,2-benzenedithiolate, dppf = 1,1-bis(diphenylphosphino)ferrocene), has been recently found to be reasonably active on proton reduction to dihydrogen (J. Am. Chem. Soc. 2015, 137, 1109). Interestingly, this exceptional complex was found to be also reactive towards dihydrogen activation as indicated by the electrochemical investigation. However, a pure nickel dithiolene diphosphine theoretical mode, excluding the contributions from iron moiety, was applied to attribute the experimental catalytic observation. We have re-visited the theoretical approach in details for this [NiFe] catalyst and compared it with the non-active nickel dithiolene diphosphine complexes. We found that both nickel and iron moieties in this newly developed complex were imperative for the observed catalytic per-formance, particularly towards the activation of dihydrogen.

  16. [NiFe] dithiolene diphosphine complex for hydrogen gas activation: a Theoretic Insight

    OpenAIRE

    2015-01-01

    A diphosphino-nickel-iron dithiolene complex, [Ni(bdt)(dppf)] (bdt = 1,2-benzenedithiolate, dppf = 1,1-bis(diphenylphosphino)ferrocene), has been recently found to be reasonably active on proton reduction to dihydrogen (J. Am. Chem. Soc. 2015, 137, 1109). Interestingly, this exceptional complex was found to be also reactive towards dihydrogen activation as indicated by the electrochemical investigation. However, a pure nickel dithiolene diphosphine theoretical mode, excluding the contribution...

  17. Trypanosoma cruzi: insights into naphthoquinone effects on growth and proteinase activity.

    Science.gov (United States)

    Bourguignon, Saulo C; Cavalcanti, Danielle F B; de Souza, Alessandra M T; Castro, Helena C; Rodrigues, Carlos R; Albuquerque, Magaly G; Santos, Dilvani O; da Silva, Gabriel Gomes; da Silva, Fernando C; Ferreira, Vitor F; de Pinho, Rosa T; Alves, Carlos R

    2011-01-01

    In this study we compared the effects of naphthoquinones (α-lapachone, β-lapachone, nor-β-lapachone and Epoxy-α-lap) on growth of Trypanosoma cruzi epimastigotes forms, and on viability of VERO cells. In addition we also experimentally analyzed the most active compounds inhibitory profile against T. cruzi serine- and cysteine-proteinases activity and theoretically evaluated them against cruzain, the major T. cruzi cysteine proteinase by using a molecular docking approach. Our results confirmed β-lapachone and Epoxy-α-lap with a high trypanocidal activity in contrast to α-lapachone and nor-β-lapachone whereas Epoxy-α-lap presented the safest toxicity profile against VERO cells. Interestingly the evaluation of the active compounds effects against T. cruzi cysteine- and serine-proteinases activities revealed different targets for these molecules. β-Lapachone is able to inhibit the cysteine-proteinase activity of T. cruzi proteic whole extract and of cruzain, similar to E-64, a classical cysteine-proteinase inhibitor. Differently, Epoxy-α-lap inhibited the T. cruzi serine-proteinase activity, similar to PMSF, a classical serine-proteinase inhibitor. In agreement to these biological profiles in the enzymatic assays, our theoretical analysis showed that E-64 and β-lapachone interact with the cruzain specific S2 pocket and active site whereas Epoxy-α-lap showed no important interactions. Overall, our results infer that β-lapachone and Epoxy-α-lap compounds may inhibit T. cruzi epimastigotes growth by affecting T. cruzi different proteinases. Thus the present data shows the potential of these compounds as prototype of protease inhibitors on drug design studies for developing new antichagasic compounds.

  18. Direct Activation of ENaC by Angiotensin II: Recent Advances and New Insights

    OpenAIRE

    Zaika, Oleg; Mamenko, Mykola; Staruschenko, Alexander; Pochynyuk, Oleh

    2013-01-01

    Angiotensin II (Ang II) is the principal effector of the renin-angiotensin-aldosterone system (RAAS). It initiates myriad processes in multiple organs integrated to increase circulating volume and elevate systemic blood pressure. In the kidney, Ang II stimulates renal tubular water and salt reabsorption causing antinatriuresis and antidiuresis. Activation of RAAS is known to enhance activity of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. In addition to its w...

  19. Appraisal of active tectonics in Hindu Kush: Insights from DEM derived geomorphic indices and drainage analysis

    Directory of Open Access Journals (Sweden)

    Syed Amer Mahmood

    2012-07-01

    The results obtained from these indices were combined to yield an index of relative active tectonics (IRAT using GIS. The average of the seven measured geomorphic indices was used to evaluate the distribution of relative tectonic activity in the study area. We defined four classes to define the degree of relative tectonic activity: class 1__very high (1.0 ≤ IRAT < 1.3; class 2__high (1.3 ≥ IRAT < 1.5; class 3—moderate (1.5 ≥ IRAT < 1.8; and class 4—low (1.8 ≥ IRAT. In view of the results, we conclude that this combined approach allows the identification of the highly deformed areas related to active tectonics. Landsat imagery and field observations also evidence the presence of active tectonics based on the deflected streams, deformed landforms, active mountain fronts and triangular facets. The indicative values of IRAT are consistent with the areas of known relative uplift rates, landforms and geology.

  20. New Insights into the Antibacterial Activity of Hydroxycoumarins against Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Liang Yang

    2016-04-01

    Full Text Available Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications. In this study, we evaluated for the first time the antibacterial activity and mechanisms of action of coumarins against the phytopathogen Ralstonia solanacearum, and investigated the effect of functional group substitution. We first tested the antibacterial activity of 18 plant-derived coumarins with different substitution patterns, and found that daphnetin, esculetin, xanthotol, and umbelliferone significantly inhibited the growth of R. solanacearum. Daphnetin showed the strongest antibacterial activity, followed by esculetin and umbelliferone, with MICs of 64, 192, and 256 mg/L, respectively, better than the archetypal coumarin with 384 mg/L. We further demonstrated that the hydroxylation of coumarins at the C-6, C-7 or C-8 position significantly enhanced the antibacterial activity against R. solanacearum. Transmission electron microscope (TEM and fluorescence microscopy images showed that hydroxycoumarins may interact with the pathogen by mechanically destroying the cell membrane and inhibiting biofilm formation. The antibiofilm effect of hydroxycoumarins may relate to the repression of flagellar genes fliA and flhC. These physiological changes in R. solanacearum caused by hydroxycoumarins can provide information for integral pathogen control. The present findings demonstrated that hydroxycoumarins have superior antibacterial activity against the phytopathogen R. solanacearum, and thus have the potential to be applied for controlling plant bacterial wilt.

  1. Insights from an observational assessment of park-based physical activity in Nanchang, China

    Directory of Open Access Journals (Sweden)

    Hong Tu

    2015-01-01

    Full Text Available Internationally, parks have been shown to be an important community asset for physical activity (PA, but little is known about the relationship between park usage and physical activity in China. The purpose of this study was to determine the association between park user characteristics and PA in Nanchang, China. In June 2014, 75,678 people were observed in eight parks over 12 days using SOPARC, a validated systematic observation tool. A logistic regression analysis was used to determine the association between PA and park user characteristics. Most park users were older adults (53.5% or adults (34.6%. Overall, 55% of park users engaged in moderate-to-vigorous physical activity (MVPA. Fewer women were observed in parks than men, but were 66% more likely to be engaged in MVPA than men. Park users were more likely to be observed in MVPA between 6–9 am and when the temperature was below 30 °C. Chinese park users were more active (55% than US studies in Tampa (30%, Chicago (49%, and Los Angeles (34%. More research is necessary to identify features of parks that are associated with greater PA so that effective interventions can be developed to promote active park use in Chinese citizens.

  2. Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking.

    Science.gov (United States)

    Islam, Barira; Sharma, Charu; Adem, Abdu; Aburawi, Elhadi; Ojha, Shreesh

    2015-01-01

    Statins are hypolipidemic drugs that are effective in the treatment of hypercholesterolemia by attenuating cholesterol synthesis in the liver via competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Recently, dietary changes associated with drug therapy have garnered attention as novel drugs to mitigate or ameliorate hypercholesterolemia. The present study was undertaken to observe different dietary polyphenols that can bind to the active site of HMGR and inhibit it. Results from the 12 dietary polyphenols tested reveal that polyphenols can bind to HMGR and block the binding of nicotinamide adenine dinucleotide phosphate (NADP(+)). We observed that the rigidity of phenolic rings prevents the polyphenols from docking to the enzyme activity site. The presence of an ester linkage between the phenolic rings in (-)-epigallocatechin-3-gallate (EGCG) and the alkyl chain in curcumin allows them to orient in the active site of the HMGR and bind to the catalytic residues. EGCG and curcumin showed binding to the active site residues with a low GRID score, which may be a potential inhibitor of HMGR. Kaempferol showed binding to HMG-CoA, but with low binding affinity. These observations provide a rationale for the consistent hypolipidemic effect of EGCG and curcumin, which has been previously reported in several epidemiological and animal studies. Therefore, this study substantiates the mechanism of polyphenols on the activity of HMGR by molecular docking and provides the impetus for drug design involving further structure-function relationship studies.

  3. Molecular Imaging Provides Novel Insights on Estrogen Receptor Activity in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Alessia Stell

    2008-11-01

    Full Text Available Estrogen receptors have long been known to be expressed in several brain areas in addition to those directly involved in the control of reproductive functions. Investigations in humans and in animal models suggest a strong influence of estrogens on limbic and motor functions, yet the complexity and heterogeneity of neural tissue have limited our approaches to the full understanding of estrogen activity in the central nervous system. The aim of this study was to examine the transcriptional activity of estrogen receptors in the brain of male and female mice. Exploiting the ERE-Luc reporter mouse, we set up a novel, bioluminescence-based technique to study brain estrogen receptor transcriptional activity. Here we show, for the first time, that estrogen receptors are similarly active in male and female brains and that the estrous cycle affects estrogen receptor activity in regions of the central nervous system not known to be associated with reproductive functions. Because of its reproducibility and sensitivity, this novel bioluminescence application stands as a candidate as an innovative methodology for the study and development of drugs targeting brain estrogen receptors.

  4. Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: Novel insights into diverse MAPK outcomes

    Directory of Open Access Journals (Sweden)

    Arias Patricia

    2011-08-01

    Full Text Available Abstract Background The yeast cell wall integrity mitogen-activated protein kinase (CWI-MAPK pathway is the main regulator of adaptation responses to cell wall stress in yeast. Here, we adopt a genomic approach to shed light on two aspects that are only partially understood, namely, the characterization of the gene functional catalog associated with CWI pathway activation and the extent to which MAPK activation correlates with transcriptional outcomes. Results A systematic yeast mutant deletion library was screened for constitutive transcriptional activation of the CWI-related reporter gene MLP1. Monitoring phospho-Slt2/Mpk1 levels in the identified mutants revealed sixty-four deletants with high levels of phosphorylation of this MAPK, including mainly genes related to cell wall construction and morphogenesis, signaling, and those with unknown function. Phenotypic analysis of the last group of mutants suggests their involvement in cell wall homeostasis. A good correlation between levels of Slt2 phosphorylation and the magnitude of the transcriptional response was found in most cases. However, the expression of CWI pathway-related genes was enhanced in some mutants in the absence of significant Slt2 phosphorylation, despite the fact that functional MAPK signaling through the pathway was required. CWI pathway activation was associated to increased deposition of chitin in the cell wall - a known survival compensatory mechanism - in about 30% of the mutants identified. Conclusion We provide new insights into yeast genes related to the CWI pathway and into how the state of activation of the Slt2 MAPK leads to different outcomes, discovering the versatility of this kind of signaling pathways. These findings potentially have broad implications for understanding the functioning of other eukaryotic MAPKs.

  5. New insight into the biological treatment by activated sludge: the role of adsorption process.

    Science.gov (United States)

    Zhang, Xiaochun; Li, Xinrun; Zhang, Qingrui; Peng, Qiuming; Zhang, Wen; Gao, Faming

    2014-02-01

    The objective of this study was to evaluate the effect of adsorption on the biological treatment process of wastewater. In the absence of substrate in the water, activated sludge developed well in the first hour, indicating that the growth of microorganism was not directly related to substrate concentration and the dissolved organic matter in the water assays were performed, no organic matter was detected out, revealing that there was no desorption in the activated sludge adsorption process. Activated sludge batch growth experiments in the presence of different adsorption capacities indicated that specific growth rate increased as specific adsorption capacity increased. The experiment on the relationship of adsorption capacity and substrate concentration or sludge concentration was also carried out. Specific adsorption capacity increased as sludge load increased, presenting linear correlation. The experiment results showed that adsorption should be taken into account in the study of the biological treatment process of wastewater.

  6. Structural insight into the recognition of complement C3 activation products by integrin receptors

    DEFF Research Database (Denmark)

    Bajic, Goran

    2015-01-01

    associated with microbes and apoptotic or necrotic cells. Complement not only protects against pathogens but also maintains body homeostasis. Activation of complement leads to cleavage of the complement proteins C4, C3 and C5, and their fragments have effector functions through binding to pathogen surfaces...... fragment C3a called anaphylatoxin. Complement leads to opsonization as the proteolytic fragment C3b becomes covalently linked to the activator surface through a reactive thioester. Self-surfaces are protected by complement regulators, whereas complement activation vividly amplifies on pathogens...... and their clearance by dendritic cells is mediated by αMβ2. The central molecule in my project, αMβ2 integrin, recognizes many diverse ligands including iC3b, but the molecular basis for such recognition was lacking. During my PhD I have obtained a major breakthrough in the dissection of iC3b interaction with αMβ2. I...

  7. An insight into synthetic Schiff bases revealing antiproliferative activities in vitro.

    Science.gov (United States)

    Sztanke, Krzysztof; Maziarka, Agata; Osinka, Anna; Sztanke, Małgorzata

    2013-07-01

    Schiff bases or azomethines are among the most important groups of biomolecules. These compounds have been found to reveal both remarkable biological activities and a variety of valuable practical applications. An interest in the exploration of novel series of synthetic Schiff bases has undoubtedly been growing due to their proven utility as attractive lead structures for the design of novel cytotoxic and cytostatic agents with a mechanism of action that sometimes differs from that of clinically authorized anticancer agents. Therefore, in the present paper we have focussed our attention on the collected synthetic simple Schiff bases of aldimine- and ketimine-types revealing anticancer activities in vitro, that have been described in the scientific literature during the last decade, and on structural variations whose affect the antiproliferative activity in sets of the designed molecules.

  8. Recent insights into the biological activities and drug delivery systems of tanshinones.

    Science.gov (United States)

    Cai, Yuee; Zhang, Wenji; Chen, Zirong; Shi, Zhi; He, Chengwei; Chen, Meiwan

    2016-01-01

    Tanshinones, the major lipid-soluble pharmacological constituents of the Chinese medicinal herb Tanshen (Salvia miltiorrhiza), have attracted growing scientific attention because of the prospective biomedical applications of these compounds. Numerous pharmacological activities, including anti-inflammatory, anticancer, and cardio-cerebrovascular protection activities, are exhibited by the three primary bioactive constituents among the tanshinones, ie, tanshinone I (TNI), tanshinone IIA (TNIIA), and cryptotanshinone (CPT). However, due to their poor solubility and low dissolution rate, the clinical applications of TNI, TNIIA, and CPT are limited. To solve these problems, many studies have focused on loading tanshinones into liposomes, nanoparticles, microemulsions, cyclodextrin inclusions, solid dispersions, and so on. In this review, we aim to offer an updated summary of the biological activities and drug delivery systems of tanshinones to provide a reference for these constituents in clinical applications.

  9. Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis.

    Science.gov (United States)

    Ruan, Jianqing; Yang, Mengbi; Fu, Peter; Ye, Yang; Lin, Ge

    2014-06-16

    Pyrrolizidine alkaloids (PAs) are natural toxins widely distributed in plants. The toxic potencies of different PAs vary significantly. PAs are mono- or diesters of necine acids with a necine base. On the basis of the necine bases, PAs are classified into three types: retronecine-type, otonecine-type, and platynecine-type. Hepatotoxic PAs contain an unsaturated necine base. PAs exert hepatotoxicity through metabolic activation by hepatic cytochromes P450s (CYPs) to generate reactive intermediates which form pyrrole-protein adducts. These adducts provide a mechanism-based biomarker to assess PA toxicity. In the present study, metabolic activation of 12 PAs from three structural types was investigated first in mice to demonstrate significant variations in hepatic metabolic activation of different PAs. Subsequently, the structural and enzymatic factors affecting metabolic activation of these PAs were further investigated by using human liver microsomes and recombinant human CYPs. Pyrrole-protein adducts were detected in the liver and blood of mice and the in vitro systems treated with toxic retronecine-type and otonecine-type PAs having unsaturated necine bases but not with a platynecine-type PA containing a saturated necine base. Retronecine-type PAs produced more pyrrole-protein adducts than otonecine-type PAs with similar necine acids, demonstrating that the structure of necine base affected PA toxic potency. Among retronecine-type PAs, open-ring diesters generated the highest amount of pyrrole-protein adducts, followed by macrocyclic diesters, while monoesters produced the least. Only CYP3A4 and CYP3A5 activated otonecine-type PAs, while all 10 CYPs studied showed the ability to activate retronecine-type PAs. Moreover, the contribution of major CYPs involved also varied significantly among retronecine-type PAs. In conclusion, our findings provide a scientific basis for predicting the toxicities of individual PAs in biological systems based on PA structural

  10. Transcranial electric stimulation (tES) and NeuroImaging: the state-of-the-art, new insights and prospects in basic and clinical neuroscience.

    Science.gov (United States)

    Soekadar, Surjo R; Herring, Jim Don; McGonigle, David

    2016-10-15

    Transcranial electric stimulation (tES) of the brain has attracted an increased interest in recent years. Yet, despite remarkable research efforts to date, the underlying neurobiological mechanisms of tES' effects are still incompletely understood. This Special Issue aims to provide a comprehensive and up-to-date overview of the state-of-the-art in studies combining tES and neuroimaging, while introducing most recent insights and outlining future prospects related to this new and rapidly growing field. The findings reported here combine methodological advancements with insights into the underlying mechanisms of tES itself. At the same time, they also point to the many caveats and specific challenges associated with such studies, which can arise from both technical and biological sources. Besides promising to advance basic neuroscience, combined tES and neuroimaging studies may also substantially change previous conceptions about the methods of action of electric or magnetic stimulation on the brain.

  11. Immunoglobulin free light chains: new insights in mast cell activation and immunology

    NARCIS (Netherlands)

    Thio, M.

    2011-01-01

    In this thesis, several studies are described that elaborate on the biological properties of immunoglobulin free light chains (Ig-fLC) related to the activation of mast cells and effects on other cells. Mast cell degranulation through Ig-fLC requires two events. At first, mast cell-bound Ig-fLCs sho

  12. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  13. XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Fan, L.; Fuss, J.O.; Cheng, Q.J.; Arvai, A.S.; Hammel, M.; Roberts, V.A.; Cooper, P.K.; Tainer, J.A.

    2009-05-18

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  14. Factor B structure provides insights into activation of the central protease of the complement system

    NARCIS (Netherlands)

    Milder, F.J.; Gomes, L.; Schouten, A.; Janssen, B.J.C.; Huizinga, E.G.; Romijn, R.A.; Hemrika, W.; Roos, A; Daha, M.R.; Gros, P.

    2007-01-01

    Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A° resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domai

  15. Marketing Activities to Support ‘Moderately Novel’ Product Innovation: Insights from the Chemical Industry

    NARCIS (Netherlands)

    Smits, A.A.J.; Vissers, G.A.N.; Dankbaar, B.

    2015-01-01

    Scholars often follow a contingency approach to study which marketing activities are suitable for a particular type of product innovation project, thereby making a distinction between incremental and radical innovation only. ‘Moderately novel’ projects, which have intermediate levels of newness, hav

  16. [Enhancing glutamate decarboxylase activity by site-directed mutagenesis: an insight from Ramachandran plot].

    Science.gov (United States)

    Ke, Piyu; Huang, Jun; Hu, Sheng; Zhao, Weirui; Lü, Changjiang; Yu, Kai; Lei, Yinlin; Wang, Jinbo; Mei, Lehe

    2016-01-01

    Glutamate decarboxylase (GAD) can catalyze the decarboxylation of glutamate into γ-aminobutyrate (GABA) and is the only enzyme of GABA biosynthesis. Improving GAD activity and thermostability will be helpful for the highly efficient biosynthesis of GABA. According to the Ramachandran plot information of GAD 1407 three-dimensional structure from Lactobacillus brevis CGMCC No. 1306, we identified the unstable site K413 as the mutation target, constructed the mutant GAD by site-directed mutagenesis and measured the thermostability and activity of the wide type and mutant GAD. Mutant K413A led to a remarkably slower inactivation rate, and its half-life at 50 °C reached 105 min which was 2.1-fold higher than the wild type GAD1407. Moreover, mutant K413I exhibited 1.6-fold higher activity in comparison with the wide type GAD1407, although it had little improvement in thermostability of GAD. Ramachandran plot can be considered as a potential approach to increase GAD thermostability and activity.

  17. Structural insights into the dehydroascorbate reductase activity of human omega-class glutathione transferases.

    Science.gov (United States)

    Zhou, Huina; Brock, Joseph; Liu, Dan; Board, Philip G; Oakley, Aaron J

    2012-07-13

    The reduction of dehydroascorbate (DHA) to ascorbic acid (AA) is a vital cellular function. The omega-class glutathione transferases (GSTs) catalyze several reductive reactions in cellular biochemistry, including DHA reduction. In humans, two isozymes (GSTO1-1 and GSTO2-2) with significant DHA reductase (DHAR) activity are found, sharing 64% sequence identity. While the activity of GSTO2-2 is higher, it is significantly more unstable in vitro. We report the first crystal structures of human GSTO2-2, stabilized through site-directed mutagenesis and determined at 1.9 Å resolution in the presence and absence of glutathione (GSH). The structure of a human GSTO1-1 has been determined at 1.7 Å resolution in complex with the reaction product AA, which unexpectedly binds in the G-site, where the glutamyl moiety of GSH binds. The structure suggests a similar mode of ascorbate binding in GSTO2-2. This is the first time that a non-GSH-based reaction product has been observed in the G-site of any GST. AA stacks against a conserved aromatic residue, F34 (equivalent to Y34 in GSTO2-2). Mutation of Y34 to alanine in GSTO2-2 eliminates DHAR activity. From these structures and other biochemical data, we propose a mechanism of substrate binding and catalysis of DHAR activity.

  18. New insight into the solution structures of wheat gluten proteins from Raman optical activity

    DEFF Research Database (Denmark)

    Blanch, E.W.; Kasarda, D.D.; Hecht, L.

    2003-01-01

    Vibrational Raman optical activity (ROA) spectra of the wheat proteins a-gliadin (A-gliadin), omega-liadin, and a 30 kDa peptide called T-A-1 from the high molecular weight glutenin subunit (HMW-GS) Dx5 were measured to obtain new information about their solution structures. The spectral data sho...

  19. Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking

    Directory of Open Access Journals (Sweden)

    Islam B

    2015-08-01

    Full Text Available Barira Islam,1,* Charu Sharma,2,* Abdu Adem,3 Elhadi Aburawi,1 Shreesh Ojha3 1Department of Paediatrics, 2Department of Internal Medicine, 3Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates *These authors contributed equally to this work Abstract: Statins are hypolipidemic drugs that are effective in the treatment of hypercholesterolemia by attenuating cholesterol synthesis in the liver via competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase. Recently, dietary changes associated with drug therapy have garnered attention as novel drugs to mitigate or ameliorate hypercholesterolemia. The present study was undertaken to observe different dietary polyphenols that can bind to the active site of HMGR and inhibit it. Results from the 12 dietary polyphenols tested reveal that polyphenols can bind to HMGR and block the binding of nicotinamide adenine dinucleotide phosphate (NADP+. We observed that the rigidity of phenolic rings prevents the polyphenols from docking to the enzyme activity site. The presence of an ester linkage between the phenolic rings in (–-epigallocatechin-3-gallate (EGCG and the alkyl chain in curcumin allows them to orient in the active site of the HMGR and bind to the catalytic residues. EGCG and curcumin showed binding to the active site residues with a low GRID score, which may be a potential inhibitor of HMGR. Kaempferol showed binding to HMG-CoA, but with low binding affinity. These observations provide a rationale for the consistent hypolipidemic effect of EGCG and curcumin, which has been previously reported in several epidemiological and animal studies. Therefore, this study substantiates the mechanism of polyphenols on the activity of HMGR by molecular docking and provides the impetus for drug design involving further structure–function relationship studies. Keywords: polyphenols

  20. Global Indicators Analysis and Consultancy Experience Insights into Correlation between Entrepreneurial Activities and Business Environment

    Directory of Open Access Journals (Sweden)

    Jovan Krivokapić

    2015-02-01

    Full Text Available Many researches and practical experiences clearly indicate the existence of a strong relationship between entrepreneurial activities and the business environment in which these activities are initiated. Although this topic has been quite ignored until the late twentieth century, a lot of studies and consulting practice have contributed to the fact that there are now a number of theories concerning mentioned correlation. These theories aim to offer a model that would provide better utilization of the possibilities from the business environment which could be very important for the development from both macroeconomic and microeconomic aspects. An increasing number of articles on this topic says enough about its importance, and numerous researches by many reputable globally recognized institutions go in favor of this claim. There are many indicators that observe the economic situation in a country or a region from different aspects, so the analyses of these indicators make it possible to determine the specific relationships between entrepreneurial activities and the local and the global business environment. Given the complexity of these relations, the impact cannot be observed partially, without taking into consideration other important factors, but more detailed analyses, however, result in some useful conclusions, which in the proper context can have a positive impact on many economic factors. It is very important to emphasize the fact that the correlation between the business environment and entrepreneurial activities is bidirectional, since this influence is mutual, so that changes in one of these factors can and usually cause some modifications in the other. Frequent series of such iterations actually lead to changes in the business environment, while entrepreneurial activity changes its shape and affects the economy of a country or a region, which is of particular importance for its competitiveness in the era of globalization.

  1. Streaming potential modeling in fractured rock: Insights into the identification of hydraulically active fractures

    CERN Document Server

    Roubinet, D; Jougnot, D; Irving, J

    2016-01-01

    Numerous field experiments suggest that the self-potential (SP) geophysical method may allow for the detection of hydraulically active fractures and provide information about fracture properties. However, a lack of suitable numerical tools for modeling streaming potentials in fractured media prevents quantitative interpretation and limits our understanding of how the SP method can be used in this regard. To address this issue, we present a highly efficient two-dimensional discrete-dual-porosity approach for solving the fluid flow and associated self-potential problems in fractured rock. Our approach is specifically designed for complex fracture networks that cannot be investigated using standard numerical methods. We then simulate SP signals associated with pumping conditions for a number of examples to show that (i) accounting for matrix fluid flow is essential for accurate SP modeling and (ii) the sensitivity of SP to hydraulically active fractures is intimately linked with fracture-matrix fluid interaction...

  2. Activities of Amphioxus GH-Like Protein in Osmoregulation: Insight into Origin of Vertebrate GH Family

    Science.gov (United States)

    Li, Mengyang; Jiang, Chengyan

    2017-01-01

    GH is known to play an important role in both growth promotion and osmoregulation in vertebrates. We have shown that amphioxus possesses a single GH-like hormone (GHl) gene encoding a functional protein capable of promoting growth. However, if GHl can mediate osmoregulation remains open. Here, we demonstrated clearly that GHl increased not only the survival rate of amphioxus but also the muscle moisture under high salinity. Moreover, GHl induced the expression of both the ion transporter Na+-K+-ATPase (NKA) and Na+-K+-2Cl− cotransporter (NKCC) in the gill as well as the mediator of GH action IGFl in the hepatic caecum, indicating that GHl fulfills this osmoregulatory activity through the same mechanisms of vertebrate GH. These results together suggest that the osmoregulatory activities of GH had emerged in the basal chordate amphioxus. We also proposed a new model depicting the origin of pituitary hormone family in vertebrates.

  3. Non-linear rheology of active particle suspensions: Insights from an analytical approach

    OpenAIRE

    Heidenreich, Sebastian; Hess, Siegfried; Klapp, Sabine H. L.

    2010-01-01

    We consider active suspensions in the isotropic phase subjected to a shear flow. Using a set of extended hydrodynamic equations we derive a variety of {\\em analytical} expressions for rheological quantities such as shear viscosity and normal stress differences. In agreement to full-blown numerical calculations and experiments we find a shear thickening or -thinning behaviour depending on whether the particles are contractile or extensile. Moreover, our analytical approach predicts that the no...

  4. Structural insight into the active site of a Bombyx mori unclassified glutathione transferase.

    Science.gov (United States)

    Hossain, Md Tofazzal; Yamamoto, Kohji

    2015-01-01

    Glutathione transferases (GSTs) are major detoxification enzymes that play central roles in the defense against various environmental toxicants as well as oxidative stress. Here, we identify amino acid residues of an unclassified GST from Bombyx mori, bmGSTu-interacting glutathione (GSH). Site-directed mutagenesis of bmGSTu mutants indicated that amino acid residues Asp103, Ser162, and Ser166 contribute to catalytic activity.

  5. Structural Insights into the Dual Activities of the Nerve Agent Degrading Organophosphate Anhydrolase/Prolidase

    Science.gov (United States)

    2009-12-11

    many pesticides used worldwide to protect crops and mammals are OP-based. Several insecticides are synthesized as “thion” (PdS bond) and activated by...substrates and stability of OPAA for decontamination of G- and V-type chemical warfare agents and pesticides . MATERIALS AND METHODS OPAA Purification and...Weir, K. M., Coppin, C. W., Williams, M. R., Selleck, M., Russell, R. J., and Oakeshott, J. G. (2004) Enzymatic bioremediation : From enzyme discovery to

  6. Active states and structure transformations in accreting white dwarfs

    Science.gov (United States)

    Boneva, Daniela; Kaygorodov, Pavel

    2016-07-01

    Active states in white dwarfs are usually associated with light curve's effects that concern to the bursts, flickering or flare-up occurrences. It is common that a gas-dynamics source exists for each of these processes there. We consider the white dwarf binary stars with accretion disc around the primary. We suggest a flow transformation modeling of the mechanisms that are responsible for ability to cause some flow instability and bring the white dwarfs system to the outburst's development. The processes that cause the accretion rate to sufficiently increase are discussed. Then the transition from a quiescent to an active state is realized. We analyze a quasi-periodic variability in the luminosity of white dwarf binary stars systems. The results are supported with an observational data.

  7. New insights into the structural bases of activation of Cys-loop receptors.

    Science.gov (United States)

    Bouzat, Cecilia

    2012-01-01

    Neurotransmitter receptors of the Cys-loop superfamily mediate rapid synaptic transmission throughout the nervous system, and include receptors activated by ACh, GABA, glycine and serotonin. They are involved in physiological processes, including learning and memory, and in neurological disorders, and they are targets for clinically relevant drugs. Cys-loop receptors assemble either from five copies of one type of subunit, giving rise to homomeric receptors, or from several types of subunits, giving rise to heteromeric receptors. Homomeric receptors are invaluable models for probing fundamental relationships between structure and function. Receptors contain a large extracellular domain that carries the binding sites and a transmembrane region that forms the ion pore. How the structural changes elicited by agonist binding are propagated through a distance of 50Å to the ion channel gate is central to understanding receptor function. Depending on the receptor subtype, occupancy of either two, as in the prototype muscle nicotinic receptor, or three binding sites, as in homomeric receptors, is required for full activation. The conformational changes initiated at the binding sites are propagated to the gate through the interface between the extracellular and transmembrane domains. This region forms a network that relays structural changes from the binding site towards the pore, and also contributes to open channel lifetime and rate of desensitization. Thus, this coupling region controls the beginning and duration of a synaptic response. Here we review recent advances in the molecular mechanism by which Cys-loop receptors are activated with particular emphasis on homomeric receptors.

  8. Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

    Science.gov (United States)

    Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

    2016-08-01

    Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

  9. Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder

    Science.gov (United States)

    Niu, Qihui; Yang, Lei; Song, Xueqin; Chu, Congying; Liu, Hao; Zhang, Lifang; Li, Yan; Zhang, Xiang; Cheng, Jingliang; Li, Youhui

    2017-01-01

    Objective This paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD. Methods Twenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample t-test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain. Results Compared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC). Conclusion OCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD. PMID:28243104

  10. A novel insight into the oxidoreductase activity of Helicobacter pylori HP0231 protein.

    Directory of Open Access Journals (Sweden)

    Paula Roszczenko

    Full Text Available BACKGROUND: The formation of a disulfide bond between two cysteine residues stabilizes protein structure. Although we now have a good understanding of the Escherichia coli disulfide formation system, the machineries at work in other bacteria, including pathogens, are poorly characterized. Thus, the objective of this work was to improve our understanding of the disulfide formation machinery of Helicobacter pylori, a leading cause of ulcers and a risk factor for stomach cancer worldwide. METHODS AND RESULTS: The protein HP0231 from H. pylori, a structural counterpart of E. coli DsbG, is the focus of this research. Its function was clarified by using a combination of biochemical, microbiological and genetic approaches. In particular, we determined the biochemical properties of HP0231 as well as its redox state in H. pylori cells. CONCLUSION: Altogether our results show that HP0231 is an oxidoreductase that catalyzes disulfide bond formation in the periplasm. We propose to call it HpDsbA.

  11. Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles

    Directory of Open Access Journals (Sweden)

    Mayank Aggarwal

    2014-03-01

    Full Text Available Human carbonic anhydrases (CAs are zinc metalloenzymes that catalyze the hydration and dehydration of CO2 and HCO3−, respectively. The reaction follows a ping-pong mechanism, in which the rate-limiting step is the transfer of a proton from the zinc-bound solvent (OH−/H2O in/out of the active site via His64, which is widely believed to be the proton-shuttling residue. The decreased catalytic activity (∼20-fold lower with respect to the wild type of a variant of CA II in which His64 is replaced with Ala (H64A CA II can be enhanced by exogenous proton donors/acceptors, usually derivatives of imidazoles and pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II in complex with four imidazole derivatives (imidazole, 1-methylimidazole, 2-methylimidazole and 4-methylimidazole have been determined and reveal multiple binding sites. Two of these imidazole binding sites have been identified that mimic the positions of the `in' and `out' rotamers of His64 in wild-type CA II, while another directly inhibits catalysis by displacing the zinc-bound solvent. The data presented here not only corroborate the importance of the imidazole side chain of His64 in proton transfer during CA catalysis, but also provide a complete structural understanding of the mechanism by which imidazoles enhance (and inhibit when used at higher concentrations the activity of H64A CA II.

  12. A proteomic insight into the effects of the immunomodulatory hydroxynaphthoquinone lapachol on activated macrophages.

    Science.gov (United States)

    Oliveira, Renato A S; Correia-Oliveira, Janaina; Tang, Li-Jun; Garcia, Rodolfo C

    2012-09-01

    We report the effect of an immunomodulatory and anti-mycobacterial naphthoquinone, lapachol, on the bi-dimensional patterns of protein expression of toll-like receptor 2 (TLR2)-agonised and IFN-γ-treated THP-1 macrophages. This non-hypothesis driven proteomic analysis intends to shed light on the cellular functions lapachol may be affecting. Proteins of both cytosol and membrane fractions were analysed. After quantification of the protein spots, the protein levels corresponding to macrophages activated in the absence or presence of lapachol were compared. A number of proteins were identified, the levels of which were appreciably and significantly increased or decreased as a result of the action of lapachol on the activated macrophages: cofilin-1, fascin, plastin-2, glucose-6-P-dehydrogenase, adenylyl cyclase-associated protein 1, pyruvate kinase, sentrin-specific protease 6, cathepsin B, cathepsin D, cytosolic aminopeptidase, proteasome β type-4 protease, tryptophan-tRNA ligase, DnaJ homolog and protein disulphide isomerase. Altogether, the comparative analysis performed indicates that lapachol could be hypothetically causing an impairment of cell migration and/or phagocytic capacity, an increase in NADPH availability, a decrease in pyruvate concentration, protection from proteosomal protein degradation, a decrease in lysosomal protein degradation, an impairment of cytosolic peptide generation, and an interference with NOS2 activation and grp78 function. The present proteomic results suggest issues that should be experimentally addressed ex- and in-vivo, to establish more accurately the potential of lapachol as an anti-infective drug. This study also constitutes a model for the pre-in-vivo evaluation of drug actions.

  13. Addressing complex healthcare problems in diverse settings: insights from activity theory.

    Science.gov (United States)

    Greig, Gail; Entwistle, Vikki A; Beech, Nic

    2012-02-01

    In the U.K., approaches to policy implementation, service improvement and quality assurance treat policy, management and clinical care as separate, hierarchical domains. They are often based on the central knowledge transfer (KT) theory idea that best practice solutions to complex problems can be identified and 'rolled out' across organisations. When the designated 'best practice' is not implemented, this is interpreted as local--particularly management--failure. Remedial actions include reiterating policy aims and tightening performance management of solution implementation, frequently to no avail. We propose activity theory (AT) as an alternative approach to identifying and understanding the challenges of addressing complex healthcare problems across diverse settings. AT challenges the KT conceptual separations between levels of policy, management and clinical care. It does not regard knowledge and practice as separable, and does not understand them in the commodified way that has typified some versions of KT theory. Instead, AT focuses on "objects of activity" which can be contested. It sees new practice as emerging from contradiction and understands knowledge and practice as fundamentally entwined, not separate. From an AT perspective, there can be no single best practice. The contributions of AT are that it enables us to understand the dynamics of knowledge-practice in activities rather than between levels. It shows how efforts to reduce variation from best practice may paradoxically remove a key source of practice improvement. After explaining the principles of AT we illustrate its explanatory potential through an ethnographic study of primary healthcare teams responding to a policy aim of reducing inappropriate hospital admissions of older people by the 'best practice' of rapid response teams.

  14. New Insights on the Mechanism of the K+-Independent Activity of Crenarchaeota Pyruvate Kinases

    Science.gov (United States)

    De la Vega-Ruíz, Gustavo; Domínguez-Ramírez, Lenin; Riveros-Rosas, Héctor; Guerrero-Mendiola, Carlos; Torres-Larios, Alfredo; Hernández-Alcántara, Gloria; García-Trejo, José J.; Ramírez-Silva, Leticia

    2015-01-01

    Eukarya pyruvate kinases have glutamate at position 117 (numbered according to the rabbit muscle enzyme), whereas in Bacteria have either glutamate or lysine and in Archaea have other residues. Glutamate at this position makes pyruvate kinases K+-dependent, whereas lysine confers K+-independence because the positively charged residue substitutes for the monovalent cation charge. Interestingly, pyruvate kinases from two characterized Crenarchaeota exhibit K+-independent activity, despite having serine at the equivalent position. To better understand pyruvate kinase catalytic activity in the absence of K+ or an internal positive charge, the Thermofilum pendens pyruvate kinase (valine at the equivalent position) was characterized. The enzyme activity was K+-independent. The kinetic mechanism was random order with a rapid equilibrium, which is equal to the mechanism of the rabbit muscle enzyme in the presence of K+ or the mutant E117K in the absence of K+. Thus, the substrate binding order of the T. pendens enzyme was independent despite lacking an internal positive charge. Thermal stability studies of this enzyme showed two calorimetric transitions, one attributable to the A and C domains (Tm of 99.2°C), and the other (Tm of 105.2°C) associated with the B domain. In contrast, the rabbit muscle enzyme exhibits a single calorimetric transition (Tm of 65.2°C). The calorimetric and kinetic data indicate that the B domain of this hyperthermophilic enzyme is more stable than the rest of the protein with a conformation that induces the catalytic readiness of the enzyme. B domain interactions of pyruvate kinases that have been determined in Pyrobaculum aerophilum and modeled in T. pendens were compared with those of the rabbit muscle enzyme. The results show that intra- and interdomain interactions of the Crenarchaeota enzymes may account for their higher B domain stability. Thus the structural arrangement of the T. pendens pyruvate kinase could allow charge

  15. Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

    Science.gov (United States)

    Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

    2014-10-01

    The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations.

  16. Nonlinear rheology of active particle suspensions: insights from an analytical approach.

    Science.gov (United States)

    Heidenreich, Sebastian; Hess, Siegfried; Klapp, Sabine H L

    2011-01-01

    We consider active suspensions in the isotropic phase subjected to a shear flow. Using a set of extended hydrodynamic equations we derive a variety of analytical expressions for rheological quantities such as shear viscosity and normal stress differences. In agreement to full-blown numerical calculations and experiments we find a shear-thickening or -thinning behavior depending on whether the particles are contractile or extensile. Moreover, our analytical approach predicts that the normal stress differences can change their sign in contrast to passive suspensions.

  17. Active reward processing during human sleep: insights from sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Lampros ePerogamvros

    2012-11-01

    Full Text Available In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED, a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity on reward-related questionnaires. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  18. Active Reward Processing during Human Sleep: Insights from Sleep-Related Eating Disorder.

    Science.gov (United States)

    Perogamvros, Lampros; Baud, Patrick; Hasler, Roland; Cloninger, Claude Robert; Schwartz, Sophie; Perrig, Stephen

    2012-01-01

    In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED), a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography, a dream diary and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  19. Neural correlates of insight in dreaming and psychosis.

    Science.gov (United States)

    Dresler, Martin; Wehrle, Renate; Spoormaker, Victor I; Steiger, Axel; Holsboer, Florian; Czisch, Michael; Hobson, J Allan

    2015-04-01

    The idea that dreaming can serve as a model for psychosis has a long and honourable tradition, however it is notoriously speculative. Here we demonstrate that recent research on the phenomenon of lucid dreaming sheds new light on the debate. Lucid dreaming is a rare state of sleep in which the dreamer gains insight into his state of mind during dreaming. Recent electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) data for the first time allow very specific hypotheses about the dream-psychosis relationship: if dreaming is a reasonable model for psychosis, then insight into the dreaming state and insight into the psychotic state should share similar neural correlates. This indeed seems to be the case: cortical areas activated during lucid dreaming show striking overlap with brain regions that are impaired in psychotic patients who lack insight into their pathological state. This parallel allows for new therapeutic approaches and ways to test antipsychotic medication.

  20. Insights into the antioxidant activity of some flavones on silver nanoparticles using the chemiluminescence method

    Energy Technology Data Exchange (ETDEWEB)

    Voicescu, Mariana, E-mail: voicescu@icf.ro [Romanian Academy, Institute of Physical Chemistry “Ilie Murgulescu”, Splaiul Independentei 202, 060021 Bucharest (Romania); Nistor, Cristina L. [Polymer Department, National R and D Institute for Chemistry and Petrochemistry ICECHIM, Splaiul Independentei 202, 060021 Bucharest (Romania); Meghea, Aurelia [University POLITEHNICA of Bucharest, Faculty of Applied Chemistry and Materials Sciences, Polizu 1, 78126 Bucharest (Romania)

    2015-01-15

    The work aims to simulate in vitro the effects caused by oxidation of five hydroxyflavones (HF) (some typical models of flavonols), (3-HF, 6-HF, 7-HF, 3,6-diHF and 3,7-diHF) on silver nanoparticles (SNPs) using the chemiluminescent system luminol–hydrogen peroxide, in phosphate buffer, pH 7.4. The contribution of bovine and human serum albumins to the antioxidant activity of the mentioned flavones, and the effect on the SNPs support, in the chemiluminescent system luminol–hydrogen peroxide, has been also investigated. The results are discussed with relevance to the oxidative stress process. - Highlights: • The effects caused by oxidation of five hydroxiflavones (HF) (3-HF, 6-HF, 7-HF, 3,6-diHF and 3,7-diHF) on silver nanoparticles (SNPs) using the chemiluminescent (CL) system luminol–hydrogen peroxide, in phosphate buffer, pH 7.4. • The contribution of bovine and human serum albumins to the antioxidant activity of the mentioned flavones, and the effect on the SNPs support, in the CL system luminol–hydrogen peroxide, are discussed. • The results have relevance to the oxidative stress process.

  1. Insights on the Phytochemical Profile (Cyclopeptides and Biological Activities of Calotropis procera Latex Organic Fractions

    Directory of Open Access Journals (Sweden)

    Thiago Lustosa Jucá

    2013-01-01

    Full Text Available Calotropis procera is a medicinal plant whose pharmacological properties are associated with its latex. Here, the Calotropis procera latex fractions were investigated in an attempt to trace its phytochemical profile and measure its anti-inflammatory and toxicity activity. The crude latex was partitioned, yielding five fractions (49.4% hexane, 5.2% dichloromethane, 2.0% ethyl acetate, 2.1% n-butanol, and 41.1% aqueous. Phytochemical screening and spectroscopy analysis revealed that dichloromethane is the most chemically diverse fraction. Triterpenes were detected in both the hexane and dichloromethane fractions, while flavonoids were detected in the dichloromethane and ethyl acetate fractions. These fractions were cytotoxic to cancer cell lines (LD50 0.05 to 3.9 μg/mL and lethal to brine shrimp (LD50 10.9 to 65.7 μg/mL. Reduced neutrophil migration in rats was observed in carrageenan-induced peritonitis for the dichloromethane (67%, ethyl acetate (56%, and aqueous (72% fractions. A positive reaction with tolidine and ninhydrin suggested that cyclopeptides are in the ethyl acetate fraction. It is therefore concluded that Calotropis procera latex dichloromethane and ethyl acetate fractions exhibit both in vitro and in vivo activities as well as anti-inflammatory properties. Cyclopeptide detection is especially interesting because previous attempts to investigate these low-molecular cyclic amino acid sequences in C. procera have failed.

  2. A Near-Atomic Structure of the Dark Apoptosome Provides Insight into Assembly and Activation.

    Science.gov (United States)

    Cheng, Tat Cheung; Akey, Ildikó V; Yuan, Shujun; Yu, Zhiheng; Ludtke, Steven J; Akey, Christopher W

    2017-01-03

    In Drosophila, the Apaf-1-related killer (Dark) forms an apoptosome that activates procaspases. To investigate function, we have determined a near-atomic structure of Dark double rings using cryo-electron microscopy. We then built a nearly complete model of the apoptosome that includes 7- and 8-blade β-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 2' carbon of the deoxyribose ring. Interestingly, β-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in the Apaf-1 apoptosome. This wider spacing may be responsible for the lack of cytochrome c binding to β-propellers in the Dark apoptosome. Our structure also highlights the roles of two loss-of-function mutations that may block Dark assembly. Finally, the improved model provides a framework to understand apical procaspase activation in the intrinsic cell death pathway.

  3. Structural and mechanistic insights into Helicobacter pylori NikR activation

    Science.gov (United States)

    Bahlawane, C.; Dian, C.; Muller, C.; Round, A.; Fauquant, C.; Schauer, K.; de Reuse, H.; Terradot, L.; Michaud-Soret, I.

    2010-01-01

    NikR is a transcriptional metalloregulator central in the mandatory response to acidity of Helicobacter pylori that controls the expression of numerous genes by binding to specific promoter regions. NikR/DNA interactions were proposed to rely on protein activation by Ni(II) binding to high-affinity (HA) and possibly secondary external (X) sites. We describe a biochemical characterization of HpNikR mutants that shows that the HA sites are essential but not sufficient for DNA binding, while the secondary external (X) sites and residues from the HpNikR dimer–dimer interface are important for DNA binding. We show that a second metal is necessary for HpNikR/DNA binding, but only to some promoters. Small-angle X-ray scattering shows that HpNikR adopts a defined conformation in solution, resembling the cis-conformation and suggests that nickel does not trigger large conformational changes in HpNikR. The crystal structures of selected mutants identify the effects of each mutation on HpNikR structure. This study unravels key structural features from which we derive a model for HpNikR activation where: (i) HA sites and an hydrogen bond network are required for DNA binding and (ii) metallation of a unique secondary external site (X) modulates HpNikR DNA binding to low-affinity promoters by disruption of a salt bridge. PMID:20089510

  4. Antioxidant activity of ferulic acid alkyl esters in a heterophasic system: a mechanistic insight.

    Science.gov (United States)

    Anselmi, Cecilia; Centini, Marisanna; Granata, Paola; Sega, Alessandro; Buonocore, Anna; Bernini, Andrea; Facino, Roberto Maffei

    2004-10-20

    The antioxidant activity of some esters of ferulic acid with the linear fatty alcohols C7, C8 (branched and linear), C9, C11, C12, C13, C15, C16, and C18 has been studied in homogeneous and heterogeneous phases. Whereas in homogeneous phase all of the alkyl ferulates possessed similar radical-scavenging abilities, in rat liver microsomes they showed striking differences, the more effective being C12 (7) (IC50 = 11.03 M), linear C8 (3) (IC50 = 12.40 microM), C13 (8) (IC50 = 18.60 microM), and C9 (5) (IC50 = 19.74 microM), followed by C7 (2), C15 (9), C11 (6), branched C8 (4), C16 (10), and C18 (11) (ferulic acid was the less active, IC50 = 243.84 microM). All of the molecules showed similar partition coefficients in an octanol-buffer system. Three-dimensional studies (NMR in solution, modeling in vacuo) indicate that this behavior might be due to a different anchorage of the molecules with the ester side chain to the microsomal phospholipid bilayer and to a consequent different orientation/positioning of the scavenging phenoxy group outside the membrane surface against the flux of oxy radicals.

  5. Structural insights into human peroxisome proliferator activated receptor delta (PPAR-delta selective ligand binding.

    Directory of Open Access Journals (Sweden)

    Fernanda A H Batista

    Full Text Available Peroxisome proliferator activated receptors (PPARs δ, α and γ are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328 in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design.

  6. New Insights into the Active Tectonics of Eastern Indonesia from GPS Measurements

    Science.gov (United States)

    Susilo, S.; Koulali Idrissi, A.; McClusky, S.; Meilano, I.; Cummins, P. R.; Tregoning, P.; Syafii, A.

    2014-12-01

    The Indonesian archipelago encompasses a wide range of tectonic environments, including island arc volcanism, subduction zones, and arc-continent collision. Many of the details of this tectonic activity are still poorly understood, especially where the Australian continent collides with Indonesia, separating the Sunda Arc in west from that at the Banda Arc in the east. While it seems clear that the Australian plate is subducted under both the Sunda and Banda Arcs, it is not clear what happens along the 1000 km -long stretch in between. The question of just where the plate motion is accommodated is of major importance to assessments of earthquake and tsunami hazard in the region. To help resolve these questions the Geospatial Information Agency of Indonesia has collaborated with the Australian National University and the Bandung Institute of Technology in a GPS campaign spanning much of eastern Indonesia, from Lombok in the west to Alor in the east. We have combined these data with those from previous campaigns, resulting in over 27 campaign and 18 continuous GPS sites being used in the analysis. The improvement in site density allowed us to develop of a more complete description of tectonic activity in this region than has been obtained in previous studies. Our preliminary results suggests that there is a relatively simple transition from subduction at the Java Trench off east Java, to a partitioned convergence along both the Timor Trough and the Flores Thrust in the Nusa Tenggara region.

  7. Immunity activation in brain cells in epilepsy: mechanistic insights and pathological consequences.

    Science.gov (United States)

    Ravizza, Teresa; Kostoula, Chrysaugi; Vezzani, Annamaria

    2013-12-01

    The search of targets for developing novel drugs that can control seizures resistant to available treatments in children and adults represents a great challenge for basic science. In the past decade, emerging evidence pointed out to the crucial role played by glia, the innate immunity brain-resident cells, in the generation of hyperexcitable neuronal networks underlying seizures. Molecular and pharmacological studies targeting glia, and the inflammatory mediators released by these cells in experimental models of epilepsy, highlighted novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments. This article will focus on the role of immunity activation in the brain and the concomitant release by glia of inflammatory molecules with neuromodulatory properties, in the pathogenesis of epileptic seizures, cell loss, and comorbidities.

  8. Recommended survey designs for occupancy modelling using motion-activated cameras: insights from empirical wildlife data.

    Science.gov (United States)

    Shannon, Graeme; Lewis, Jesse S; Gerber, Brian D

    2014-01-01

    Motion-activated cameras are a versatile tool that wildlife biologists can use for sampling wild animal populations to estimate species occurrence. Occupancy modelling provides a flexible framework for the analysis of these data; explicitly recognizing that given a species occupies an area the probability of detecting it is often less than one. Despite the number of studies using camera data in an occupancy framework, there is only limited guidance from the scientific literature about survey design trade-offs when using motion-activated cameras. A fuller understanding of these trade-offs will allow researchers to maximise available resources and determine whether the objectives of a monitoring program or research study are achievable. We use an empirical dataset collected from 40 cameras deployed across 160 km(2) of the Western Slope of Colorado, USA to explore how survey effort (number of cameras deployed and the length of sampling period) affects the accuracy and precision (i.e., error) of the occupancy estimate for ten mammal and three virtual species. We do this using a simulation approach where species occupancy and detection parameters were informed by empirical data from motion-activated cameras. A total of 54 survey designs were considered by varying combinations of sites (10-120 cameras) and occasions (20-120 survey days). Our findings demonstrate that increasing total sampling effort generally decreases error associated with the occupancy estimate, but changing the number of sites or sampling duration can have very different results, depending on whether a species is spatially common or rare (occupancy = ψ) and easy or hard to detect when available (detection probability = p). For rare species with a low probability of detection (i.e., raccoon and spotted skunk) the required survey effort includes maximizing the number of sites and the number of survey days, often to a level that may be logistically unrealistic for many studies. For common species with

  9. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    Science.gov (United States)

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  10. Activation energy spectra: insights into transport limitations of organic semiconductors and photovoltaic cells

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Ziqi; Nardes, Alexandre M.; Van de Lagemaat, Jao; Gregg, Brian A. [National Renewable Energy Laboratory, Golden, CO (United States)

    2012-03-07

    Some mechanisms of charge transport in organic semiconductors and organic photovoltaic (OPV) cells can be distinguished by their predicted change in activation energy for the current, E{sub a}, versus applied field, F. E{sub a} versus F is measured first in pure films of commercially available regioregular poly(3-hexylthiophene) (P3HT) and in the same P3HT treated to reduce its charged defect density. The former shows a Poole-Frenkel (PF)-like decrease in E{sub a} at low F, which then plateaus at higher F. The low defect material does not exhibit PF behavior and E{sub a} remains approximately constant. Upon addition of [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM), however, both materials show a large increase in E{sub a} and exhibit PF-like behavior over the entire field range. These results are explained with a previously proposed model of transport that considers both the localized random disorder in the energy levels and the long-range electrostatic fluctuations resulting from charged defects. Activation energy spectra in working OPV cells show that the current is injection-limited over most of the voltage range but becomes transport-limited, with a large peak in E{sub a}, near the open circuit photovoltage. This causes a decrease in fill factor, which may be a general limitation in such solar cells. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. A Framework for Detecting Fraudulent Activities in EDO State Tax Collection System Using Investigative Data Mining

    Directory of Open Access Journals (Sweden)

    Okoro F. M

    2016-05-01

    Full Text Available Edo State Inland Revenue Services is overwhelmed with gigabyte of disk capacity containing data about tax payers’ in the state. The data stored on the database increases in size at an alarming rate. This has resulted in a data rich but information poor situation where there is a widening gap between the explosive growth of data and its types, and the ability to analyze and interpret it effectively; hence the need for a new generation of automated and intelligent tools and techniques known as investigative data mining, to look for patterns in data. These patterns can lead to new insights, competitive advantages for business, and tangible benefits for the State Revenue services. This research work focuses on designing effective fraud detection and deterring architecture using investigative data mining technique. The proposed system architecture is designed to reason using Artificial Neural Network and Machine learning algorithm in order to detect and deter fraudulent activities. We recommend that the architectural framework be developed using Object Oriented Programming and Agent Oriented Programming Languages.

  12. Always connected: a first insight into the influence of smartphone adoption on the activity-travel behaviour of mobile professionals in Indonesia

    Directory of Open Access Journals (Sweden)

    Gloriani Novita Christin

    2014-10-01

    Full Text Available Purpose: The widespread adoption of smartphone, which is the result of convergence of Information and Communication Technology, potentially influence work activity of mobile professional: how they plan and execute the agenda, include how they still work during their travel. This paper aimed to gain the first insight to understand the behavioural changes in activity and travel pattern of mobile professional.Design: Cross-sectional survey that consists of 20 interviews and 50 questionnaires conducted to provide initial overview of the transformations that occur in mobile work in Indonesia, as a developing country. Simulation using the stated adaptation approach conducted to obtain a basic response patterns that occur when information is received during the ongoing daily activities.  Findings: Smartphone adoption has provided mobile professional with the ability to work in novel way. They use smartphone as an information and communication tool throughout the day to improve the productivity and to assure the efficiency of their “travelling”, as a part of their mobile work. Research limitations: Ideally, to obtain the transformation rules of travel patterns, this study should be conducted with a larger sample size. This study uses only a limited number of samples, because only intended to provide initial overview.Practical implications: the basic pattern rule of the transformation is a useful to give a better understanding   Originality/Value: By choosing Indonesia as a case study, it will be given an overview ternaformasi that occurs as a result of the adoption of smartphones in the mobile work activities in developing countries.    Research type: General Review

  13. New insights into the anti-obesity activity of xanthones from Garcinia mangostana.

    Science.gov (United States)

    Liu, Qian-Yu; Wang, Yi-Tao; Lin, Li-Gen

    2015-02-01

    Obesity has reached epidemic proportions worldwide. This condition, and its related diseases such as diabetes and cardiovascular diseases, have become major public health challenges. Fruits are important dietary components, and bioactive constituents from fruits are considered to be a promising source for developing effective and safe anti-obesity drugs. Garcinia mangostana Linn. (Clusiaceae) is a tropical evergreen tree, and its fruit, mangosteen, is called 'Queen of Fruit'. The pericarp of G. mangostana has been used for centuries in Southeast Asia as a medicinal agent for treatment of various diseases. Products derived from mangosteen are widely consumed to ameliorate metabolic dysfunction and resultant metabolic syndrome. However, the chemical principles and mechanisms underlying these effects are unclear. This review summarizes the recent chemical and pharmacological studies related to G. mangostana, including weight reduction, anti-adipogenesis, anti-inflammation and anti-oxidation activity. The aim of this review is to shed light on the role of G. mangostana and its constituents in preventing and treating obesity, which should encourage more interest in the development of relevant therapeutic methods.

  14. New Insights on Late-A and Early-F Star Activity

    Science.gov (United States)

    Freire Ferrero, R.; Catalano, S.; Marilli, E.; Gouttebroze, P.; Talavera, A.; Bruhweiler, F.

    The onset of chromospheric activity in late-A and early-F stars is here discussed. The detection of Ly- emission core in several A and F atars with the IUE satellite, gives evidence for the presence of chromospheric layers in these stars up to B - V = 0m.19 (Marilli et al., 1996). Semiempirical chromospheric models for Altair allowed us (Freire Ferrero et al., 1995) to explain the observed emission profiles taking into account normal H I interstellar (IS) absorption. However, due to the very high rotational velocity, we analysed alternative hypotheses to explain the observed emissions: (1) circumstellar or shell matter; (2) co-rotating expanding optically thin wind. We ruled out these hypotheses because their effects are negligible and as a consequence, this result reinforces the chromospheric origin of the observed Ly- core in Altair. The stars of our sample, having observed Ly- profilies similar to Altair's and similar stellar and IS properties, should reproduce similar chromospheric behaviour. Here we discuss several important questions that are raised by these results.

  15. Ordering Dynamics in Neuron Activity Pattern Model: An Insight to Brain Functionality.

    Science.gov (United States)

    Gundh, Jasleen; Singh, Awaneesh; Singh, R K Brojen

    2015-01-01

    We study the domain ordering kinetics in d = 2 ferromagnets which corresponds to populated neuron activities with both long-ranged interactions, V(r) ∼ r-n and short-ranged interactions. We present the results from comprehensive Monte Carlo (MC) simulations for the nonconserved Ising model with n ≥ 2, interaction range considering near and far neighbors. Our model results could represent the long-ranged neuron kinetics (n ≤ 4) in consistent with the same dynamical behaviour of short-ranged case (n ≥ 4) at far below and near criticality. We found that emergence of fast and slow kinetics of long and short ranged case could imitate the formation of connections among near and distant neurons. The calculated characteristic length scale in long-ranged interaction is found to be n independent (L(t) ∼ t1/(n-2)), whereas short-ranged interaction follows L(t) ∼ t1/2 law and approximately preserve universality in domain kinetics. Further, we did the comparative study of phase ordering near the critical temperature which follows different behaviours of domain ordering near and far critical temperature but follows universal scaling law.

  16. New insights into dietary supplements used in sport: active substances, pharmacological and side effects.

    Science.gov (United States)

    Koncic, Marijana Zovko; Tomczyk, Michal

    2013-08-01

    As a society we are increasingly concerned about our physical appearance. For example, as much as 24% of people in developed countries admittedly exercise to improve their performance. Professional sportsmen and amateurs alike are in a constant search for new means that will enable them better sport results in shorter time. Among those means, a prominent place belongs to dietary supplements. However, the producers often advertise products whose use in sports is neither scientifically founded nor safe. This brings on an irrational use of herbal supplements which sometimes leads to unwanted side effects, but is more often of little use. Thus, the aim of this review will be to systematically evaluate some of the herbal supplements that are used as adaptogenic and ergogenic aids in sport. The review will include available data on Rhodiola rosea, Withania somnifera, Schisandra chinensis, Tribulus terrestris, Vitis vinifera, Citrus aurantium, and others. Their effects, active ingredients as well as possible adverse effects will be discussed with special focus on clinical studies.

  17. Plasmodium falciparum Plasmepsin V (PfPMV): Insights into recombinant expression, substrate specificity and active site structure.

    Science.gov (United States)

    Boonyalai, Nonlawat; Sittikul, Pichamon; Yuvaniyama, Jirundon

    2015-05-01

    Plasmepsin V from Plasmodium falciparum (PfPMV) is responsible for the cleavage of the Plasmodium export element (PEXEL) motif at the N-terminus of several hundreds of the exported proteins. PfPMV is necessary for parasite viability and has become a novel promising target for antimalarial therapy. The first recombinant expression of soluble, active PfPMV as thioredoxin fusion proteins is reported herein. Two truncated forms of PfPMV were fused to thioredoxin (Trx) to generate Trx-PfPMVp37 and Trx-PfPMVm84. The fusion proteins were successfully purified using Ni(2+) affinity chromatography in combination with ATP treatment to eliminate Escherichia coli HSP60 contaminant. Trx-PfPMVm84 could hydrolyze the PEXEL-containing peptides more efficiently than Trx-PfPMVp37. Interestingly, both Trx-PfPMVs preferred to cleave PfEMP2 peptide over HRPII peptide. The replacement of Ser with Val or Glu at P1' position created a substrate with 75% reduction in the enzyme activity, whereas the substitution of Ile with Lys or Glu at P2 position reduced the cleavage efficiency by 30%. The activity of Trx-PfPMVm84 was inhibited by PMSF and nelfinavir but not by pepstatin A. After the removal of Trx domain, activities of both enzymes toward PfEMP2 and HRPII peptides were fitted to the Michaelis-Menten model to determine kinetic parameters. The Km values toward both peptides were apparently much lower than the previously reported data although with similar kcat values. Along with an improved PfPMV preparation protocol, these findings have provided insights into its substrate specificity at P2 and P1' positions as well as interactions among the enzyme, substrates, and inhibitors.

  18. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Siyu [Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Ren, Honglei; Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2015-09-15

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t{sub d,E}) and hydroxyl-radical oxidation half-lives (t{sub ·OH,E}) in sunlit surface waters. The t{sub d,E} values range from 0.56 min to 28.8 min at 45° N latitude, whereas t{sub ·OH,E} ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways.

  19. Biogeochemical Activity of Siderophilic Cyanobacteria and Insights from their Genomes Implications for the Development of New Biosignatures

    Science.gov (United States)

    Brown, I. I.; Bryant, D. A.; Thomas,-Keprta, K. L.; Tringe, S. G.; Sarkisova, S. A.; Galindo, C., Jr.; Malley, K.; Sosa, O.; Garrison, D. H.; McKay, David S.

    2010-01-01

    Verifying the links between genomie features in living organisms and their mineralization/demineralization activity will help to reveal traces of life on Earth and beyond. Among contemporary environments, iron-depositing hot springs (IDHS) may represent one of the most appropriate natural models for insights into ancient life since organisms may have originated on Earth and possibly Mars in association with hydrothennal activity and high [Fe(2+)]. Siderophilic or "iron-loving" cyanobacteria (CB) inhabiting IDHS may have genomic features and properties similar to those of ancient organisms because abundant Fe(2+) in IDHS has a strong potential to increase the magnitude of oxidative stress. That is why specific and/or additional proteins involved in Fe mineralization by siderophilic CB are expected. Inorganic polyphosphates (PPi) are known to increase the viability of prokaryotes Linder heavy metal concentrations and UV stress conditions. PPi have also been proposed as biosignatures. Ancient CB could have also been stressed by occasional migrations from the Fe(2+) rich Ocean to the basaltic land which was almost devoid of dissolved Fe(2+). Thus, the study of the adaptation reactions of siderophilic CB to fluctuation of dissolved Fe level may shed light on the paleophysiology of ancient oxygenic prokaryotes. Moreover, bioweathered Fe, Al, P, Cu, Ti and rare earth elements can be thought of as candidate organomarkers that document the effects of or ganic molecules in weathered rocks. However, the molecular mechanisms of the maintenance of Fe homeostasis in siderophilic CB, the role of PPi for this process and bioweathering activities are poorly understood. Here we present preliminary results describing a new mechanism of Fe mineralization in siderophilic CB, the effect of Fe on the generation of PPi bodies in siderophilic CB, their bioweathering activity and preliminary analysis of the diversity of proteins involved in the prevention of oxidative stress in phototrophs

  20. Insight into the Amino-Type Excited-State Intramolecular Proton Transfer Cycle Using N-Tosyl Derivatives of 2-(2'-Aminophenyl)benzothiazole.

    Science.gov (United States)

    Chen, Chi-Lin; Tseng, Huan-Wei; Chen, Yi-An; Liu, Jun-Qi; Chao, Chi-Min; Liu, Kuan-Miao; Lin, Tzu-Chieh; Hung, Cheng-Hsien; Chou, Yen-Lin; Lin, Ta-Chun; Chou, Pi-Tai

    2016-02-25

    Studies have been carried out to gain insight in to an overall excited-state proton transfer cycle for a series of N-tosyl derivatives of 2-(2'-aminophenyl)benzothiazole. The results indicate that followed by ultrafast (benzothiazole (PBT-NHTs) the subsequent cis-trans isomerization process in both triplet and ground states are probed by nanosecond transient absorption (TA) and two-step laser-induced fluorescence (TSLIF) spectroscopy. Both TA and TSLIF results indicate the existence of a long-lived trans-tautomer species in the ground state with a lifetime of few microseconds. The experimental results correlate well with the theoretical approach, which suggests that PBT-NHTs proton transfer tautomer generated in the excited state undergoes intramolecular C1-C1' rotation to ∼100° between benzothiazole and phenyl moieties in which the energetics for the S1 and T1 states are nearly identical. As a result, the intersystem crossing between S1 and T1 states serves as a fast deactivation pathway for the excited-state cis-tautomer to channel into both cis- and trans-tautomer in their respective T1 states, followed by the dominant T1-S0 radiationless deactivation to populate the trans-tautomer in the ground state. The trans-tautomer species in the S0 state proceeds with intermolecular double proton transfer to regenerate the cis-normal form. An overall proton-transfer cycle describing the amino-type ESIPT and the subsequent isomerization processes is thus depicted in detail.

  1. Structural Insights into the Activation and Inhibition of Histo-Aspartic Protease from Plasmodium falciparum

    Energy Technology Data Exchange (ETDEWEB)

    Bhaumik, Prasenjit; Xiao, Huogen; Hidaka, Koushi; Gustchina, Alla; Kiso, Yoshiaki; Yada, Rickey Y.; Wlodawer, Alexander (Guelph); (Kyoto); (NCI)

    2012-09-17

    Histo-aspartic protease (HAP) from Plasmodium falciparum is a promising target for the development of novel antimalarial drugs. The sequence of HAP is highly similar to those of pepsin-like aspartic proteases, but one of the two catalytic aspartates, Asp32, is replaced with histidine. Crystal structures of the truncated zymogen of HAP and of the complex of the mature enzyme with inhibitor KNI-10395 have been determined at 2.1 and 2.5 {angstrom} resolution, respectively. As in other proplasmepsins, the propeptide of the zymogen interacts with the C-terminal domain of the enzyme, forcing the N- and C-terminal domains apart, thereby separating His32 and Asp215 and preventing formation of the mature active site. In the inhibitor complex, the enzyme forms a tight domain-swapped dimer, not previously seen in any aspartic proteases. The inhibitor is found in an unprecedented conformation resembling the letter U, stabilized by two intramolecular hydrogen bonds. Surprisingly, the location and conformation of the inhibitor are similar to those of the fragment of helix 2 comprising residues 34p-38p in the prosegments of the zymogens of gastric aspartic proteases; a corresponding helix assumes a vastly different orientation in proplasmepsins. Each inhibitor molecule is in contact with two molecules of HAP, interacting with the carboxylate group of the catalytic Asp215 of one HAP protomer through a water molecule, while also making a direct hydrogen bond to Glu278A' of the other protomer. A comparison of the shifts in the positions of the catalytic residues in the inhibitor complex presented here with those published previously gives further hints regarding the enzymatic mechanism of HAP.

  2. Insights into functional tea infused-chitosan hydrogels as potential bio-active restorative materials

    Directory of Open Access Journals (Sweden)

    Tamara V Perchyonok

    2014-01-01

    Full Text Available Introduction: We described novel chitosan hydrogels (chitosan-H containing tea infusions (green, red and black as functional additive prototypes with special focus on the design and functionality of dual action composite restorative materials. Their intended uses include remineralizing bases/liners, therapeutically active restorative materials and/or functional additives as well as functional prototype of the drug delivery system. Materials and Methods: The above mentioned hydrogels were prepared by dispersion of the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology scanning electron microscope (SEM, release behavior (physiological pH as well as acidic conditions, stability of the hydrogels as well as antioxidant capacity of the tea infused hydrogels was evaluated. Results: It was found that all the anti-oxidant chitosan-H hydrogels treated dentine gave significantly (P < 0.05; Non-parametric ANOVA test higher shear bond strength values than dentine treated or not treated with phosphoric acid. Overall, there was a small relapse in the shear bond strength after 6 months. The SEM is employed to observe the surface of the newly made functional restorative materials. The anti-oxidant capacity of various black, red and green tea infusions was investigated and demonstrated increased antioxidant stability of the newly prepared material stability. Conclusion: We have developed and evaluated several functional chitosan hydrogels with several targets as therapeutic restorative materials, the added benefits of their unique functionality involve increased dentin adhesive bond strengths (after 24 h and after 6 month, concept of using functional materials as carriers for pro-drugs as well as display certain degree of defense mechanism for a free radical damage.

  3. Learning shapes spontaneous activity itinerating over memorized states.

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    Tomoki Kurikawa

    Full Text Available Learning is a process that helps create neural dynamical systems so that an appropriate output pattern is generated for a given input. Often, such a memory is considered to be included in one of the attractors in neural dynamical systems, depending on the initial neural state specified by an input. Neither neural activities observed in the absence of inputs nor changes caused in the neural activity when an input is provided were studied extensively in the past. However, recent experimental studies have reported existence of structured spontaneous neural activity and its changes when an input is provided. With this background, we propose that memory recall occurs when the spontaneous neural activity changes to an appropriate output activity upon the application of an input, and this phenomenon is known as bifurcation in the dynamical systems theory. We introduce a reinforcement-learning-based layered neural network model with two synaptic time scales; in this network, I/O relations are successively memorized when the difference between the time scales is appropriate. After the learning process is complete, the neural dynamics are shaped so that it changes appropriately with each input. As the number of memorized patterns is increased, the generated spontaneous neural activity after learning shows itineration over the previously learned output patterns. This theoretical finding also shows remarkable agreement with recent experimental reports, where spontaneous neural activity in the visual cortex without stimuli itinerate over evoked patterns by previously applied signals. Our results suggest that itinerant spontaneous activity can be a natural outcome of successive learning of several patterns, and it facilitates bifurcation of the network when an input is provided.

  4. Incipient mantle delamination, active tectonics and crustal thickening in Northern Morocco: Insights from gravity data and numerical modeling

    Science.gov (United States)

    Baratin, Laura-May; Mazzotti, Stéphane; Chéry, Jean; Vernant, Philippe; Tahayt, Abdelilah; Mourabit, Taoufik

    2016-11-01

    The Betic-Rif orocline surrounding the Alboran Sea, the westernmost tip of the Mediterranean Sea, accommodates the NW-SE convergence between the Nubia and Eurasia plates. Recent GPS observations indicate a ∼4 mm/yr SW motion of the Rif Mountains, relative to stable Nubia, incompatible with a simple two-plate model. New gravity data acquired in this study define a pronounced negative Bouguer anomaly south of the Rif, interpreted as a ∼40 km-thick crust in a state of non-isostatic equilibrium. We study the correlation between these present-day kinematic and geodynamic processes using a finite-element code to model in 2-D the first-order behavior of a lithosphere affected by a downward normal traction (representing the pull of a high-density body in the upper mantle). We show that intermediate viscosities for the lower crust and uppermost mantle (1021-1022Pas) allow an efficient coupling between the mantle and the base of the brittle crust, thus enabling (1) the conversion of vertical movement, resulting from the downward traction, to horizontal movement and (2) shortening in the brittle upper crust. Our results show that incipient delamination of the Nubian continental lithosphere, linked to slab pull, can explain the present-day abnormal tectonics, contribute to the gravity anomaly observed in northern Morocco, and give insight into recent tectonics in the Western Mediterranean region.

  5. The oligomeric state of the active Vps4 AAA ATPase

    Science.gov (United States)

    Monroe, Nicole; Han, Han; Gonciarz, Malgorzata D.; Eckert, Debra M.; Karren, Mary Anne; Whitby, Frank G.; Sundquist, Wesley I.; Hill, Christopher P.

    2013-01-01

    The cellular ESCRT pathway drives membrane constriction toward the cytosol and effects membrane fission during cytokinesis, endosomal sorting, and the release of many enveloped viruses, including HIV. A component of this pathway, the AAA ATPase Vps4, provides energy for pathway progression. Although it is established that Vps4 functions as an oligomer, subunit stoichiometry and other fundamental features of the functional enzyme are unclear. Higher-order oligomers have thus far only been characterized for a Walker B mutant of Vps4 in the presence of ATP. Here, we report that although some mutant Vps4 proteins form dodecameric assemblies, active wild-type S. cerevisiae and S. solfataricus Vps4 enzymes can form hexamers in the presence of ATP and ADP, as assayed by size exclusion chromatography and equilibrium analytical ultracentifugation. The Vta1p activator binds hexameric yeast Vps4p without changing the oligomeric state of Vps4p, implying that the active Vta1p:Vps4p complex also contains a single hexameric ring. Additionally, we report crystal structures of two different archaeal Vps4 homologs, whose structures and lattice interactions suggest a conserved mode of oligomerization. Disruption of the proposed hexamerization interface by mutagenesis abolished the ATPase activity of archaeal Vps4 proteins and blocked Vps4p function in S. cerevisiae. These data challenge the prevailing model that active Vps4 is a double ring dodecamer, and argue that, like other type I AAA ATPases, Vps4 functions as a single ring with six subunits. PMID:24161953

  6. A state-of-the-art assessment of active structures

    Science.gov (United States)

    1992-09-01

    A state-of-the-art assessment of active structures with emphasis towards the applications in aeronautics and space is presented. It is felt that since this technology area is growing at such a rapid pace in many different disciplines, it is not feasible to cover all of the current research but only the relevant work as relates to aeronautics and space. Research in smart actuation materials, smart sensors, and control of smart/intelligent structures is covered. In smart actuation materials, piezoelectric, magnetostrictive, shape memory, electrorheological, and electrostrictive materials are covered. For sensory materials, fiber optics, dielectric loss, and piezoelectric sensors are examined. Applications of embedded sensors and smart sensors are discussed.

  7. Activities of binary baths with 1% solute as standard states

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The relationships of activities with 1% solute as standard state and mass fraction of solute, and hot-dip temperature, were given on the base of Miedema's model, Tanaka expression, some basic thermodynamic relationships; and discussion was carried out on Zn-Mn and Zn-Ti binary alloys by calculation, in which varied colors can be achieved on the hot-dip steel sheets. The results indicate that the activity of solute shows positive deviation relative to Henry's law for both Zn-Mn and Zn-Ti binary dilute solution. The degree of deviation increases with increasing solute and decreases with increasing bath temperature. As the solution is very dilute solution (w(Mn)≤40% for Zn-Mn alloy,w(Ti)≤8% for Zn-Ti alloy), the two binary baths can all be treated as ideal dilute solutions.

  8. Design, synthesis and insight into the structure-activity relationship of 1,3-disubstituted indazoles as novel HIF-1 inhibitors.

    Science.gov (United States)

    An, Hongchan; Kim, Nam-Jung; Jung, Jong-Wha; Jang, Hannah; Park, Jong-Wan; Suh, Young-Ger

    2011-11-01

    Design, synthesis and insight into the structure-activity relationship (SAR) of 1,3-disubstituted indazoles as novel HIF-1 inhibitors are described. In particular, the substituted furan moiety on indazole skeleton as well as its substitution pattern turns out crucial for the high HIF-1 inhibition.

  9. Dog Walking and Physical Activity in the United States

    Directory of Open Access Journals (Sweden)

    Sandra A. Ham, MS

    2006-03-01

    Full Text Available Introduction Dog walking is a purposeful physical activity that may have health benefits for humans and canines. A descriptive epidemiology of the contribution of dog walking to physically active lifestyles among dog walkers in the United States has not been previously reported. Methods Data on youth and adults who reported walking for pet care trips (N = 1282 on the National Household Travel Survey 2001 were analyzed for number of trips, proportion walking a dog for at least 10 minutes on one trip, and accumulation of 30 minutes or more in 1 day of walks lasting at least 10 minutes. Results In 1 day, 58.9% of dog walkers took two or more walks, 80.2% took at least one walk of 10 minutes or more, and 42.3% accumulated 30 minutes or more from walks lasting at least 10 minutes each. There were no significant differences by sex, family income, or categories of urbanization. Conclusion Walking a dog may contribute to a physically active lifestyle and should be promoted as a strategy that fits within the framework set forth by the Task Force on Community Preventive Services for Physical Activity.

  10. Role of ELA region in auto-activation of mutant KIT receptor: a molecular dynamics simulation insight.

    Science.gov (United States)

    Purohit, Rituraj

    2014-01-01

    KIT receptor is the prime target in gastrointestinal stromal tumor (GISTs) therapy. Second generation inhibitor, Sunitinib, binds to an inactivated conformation of KIT receptor and stabilizes it in order to prevent tumor formation. Here, we investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting molecular dynamics simulation (∼100 ns). We analyzed different properties such as root mean square cutoff or deviation, root mean square fluctuation, radius of gyration, solvent-accessible surface area, hydrogen bonding network analysis, and essential dynamics. Apart from this, clustering and cross-correlation matrix approach was used to explore the conformational space of the wild type and mutant EAL region of KIT receptor. Molecular dynamics analysis indicated that mutation (D816H) was able to alter intramolecular hydrogen bonding pattern and affected the structural flexibility of EAL region. Moreover, flexible secondary elements, specially, coil and turns were dominated in EAL region of mutant KIT receptor during simulation. This phenomenon increased the movement of EAL region which in turn helped in shifting the equilibrium towards the active kinase conformation. Our atomic investigation of mutant KIT receptor which emphasized on EAL region provided a better insight into the understanding of Sunitinib resistance mechanism of KIT receptor and would help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.

  11. Insights on the role of accurate state estimation in coupled model parameter estimation by a conceptual climate model study

    Science.gov (United States)

    Yu, Xiaolin; Zhang, Shaoqing; Lin, Xiaopei; Li, Mingkui

    2017-03-01

    The uncertainties in values of coupled model parameters are an important source of model bias that causes model climate drift. The values can be calibrated by a parameter estimation procedure that projects observational information onto model parameters. The signal-to-noise ratio of error covariance between the model state and the parameter being estimated directly determines whether the parameter estimation succeeds or not. With a conceptual climate model that couples the stochastic atmosphere and slow-varying ocean, this study examines the sensitivity of state-parameter covariance on the accuracy of estimated model states in different model components of a coupled system. Due to the interaction of multiple timescales, the fast-varying atmosphere with a chaotic nature is the major source of the inaccuracy of estimated state-parameter covariance. Thus, enhancing the estimation accuracy of atmospheric states is very important for the success of coupled model parameter estimation, especially for the parameters in the air-sea interaction processes. The impact of chaotic-to-periodic ratio in state variability on parameter estimation is also discussed. This simple model study provides a guideline when real observations are used to optimize model parameters in a coupled general circulation model for improving climate analysis and predictions.

  12. GPi oscillatory activity differentiates tics from the resting state, voluntary movements, and the unmedicated parkinsonian state

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    Joohi Jimenez-Shahed

    2016-09-01

    Full Text Available Background: Deep brain stimulation (DBS is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS. Thalamic (Cm-Pf and pallidal (including globus pallidus interna, GPi targets have been the most investigated. While the neurophysiological correlates of Parkinson’s disease (PD in the GPi and subthalamic nucleus (STN are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC between beta band and high frequency oscillations (HFOs within the STN in PD patients is pathologic. Methods: We recorded intraoperative local field potentials (LFPs from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest. Results: In all PD patients, we noted excessive beta band activity (13-30Hz at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200-400Hz, indicating the presence of beta-HFO CFC. In all 3 TS patients at rest, we observed theta band activity (4-7Hz and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200-400Hz and gamma band (35-200Hz activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5-10Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects. Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting

  13. GPi Oscillatory Activity Differentiates Tics from the Resting State, Voluntary Movements, and the Unmedicated Parkinsonian State

    Science.gov (United States)

    Jimenez-Shahed, Joohi; Telkes, Ilknur; Viswanathan, Ashwin; Ince, Nuri F.

    2016-01-01

    Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic. Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest. Results: In all PD patients, we noted excessive beta band activity (13–30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4–7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200–400 Hz) and gamma band (35–200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5–10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects. Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics

  14. Resting-state brain activity in adult males who stutter.

    Directory of Open Access Journals (Sweden)

    Yun Xuan

    Full Text Available Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI, few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF, region of interest (ROI-based functional connectivity (FC and independent component analysis (ICA-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN and in the connections between them.

  15. What should be the roles of conscious states and brain states in theories of mental activity?

    Directory of Open Access Journals (Sweden)

    Donelson E Dulany

    2011-03-01

    Full Text Available Answers to the title's question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and "free will" in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness?

  16. Histopathological and molecular insights into the ovicidal activities of two entomopathogenic fungi against two-spotted spider mite.

    Science.gov (United States)

    Zhang, Lei; Shi, Wei-Bing; Feng, Ming-Guang

    2014-03-01

    Entomopathogenic fungi can infect and kill spider mite eggs but their ovicidal activities are poorly understood. Here we gain histopathogenical and molecular insights into the ovicidal activities of Beauveria bassiana and Isaria fumosorosea against the two-spotted spider mite, Tetranychus urticae. Scanning electronic microscopy indicated successful adhesion and germination of fungal conidia on egg shell at 24h post-spray (HPS). Germ tubes of both fungi could penetrate into egg shell with penetration pegs at 48 HPS. Interestingly, the germ tubes of B. bassiana may elongate on egg surface to locate appropriate sites for penetration, acting as 'searching' hyphae. Aside from the normal penetration, the germ tubes of I. fumosorosea can be completely or partially embedded into egg shell for a distance of extension, forming shell humps. Light microscopy of ultrathin sections of infected eggs showed shrunken (affected) or disrupted embryos at 48-96 HPS despite little effect on egg cleavage at 24 HPS. However, distinguishable hyphal cells were hardly found inside the embryos lacking oxygen although fungal outgrowths were abundant on unhatched (killed) eggs. In PCR with specific probes, the 18S rDNA signals of B. bassiana (412 bp) and I. fumosorosea (454 bp) in the DNA extracts from surface-cleaned mite eggs increased at 0-96 HPS, confirming fungal colonization in the infected eggs. We consider that the colonization on shell surface and underside could rely upon extending hyphae for uptake of egg nutrition, resulting in embryo disruption. Our observations add knowledge to microbial control of spider mites.

  17. Resting-state EEG theta activity and risk learning: sensitivity to reward or punishment?

    Science.gov (United States)

    Massar, Stijn A A; Kenemans, J Leon; Schutter, Dennis J L G

    2014-03-01

    Increased theta (4-7 Hz)-beta (13-30 Hz) power ratio in resting state electroencephalography (EEG) has been associated with risky disadvantageous decision making and with impaired reinforcement learning. However, the specific contributions of theta and beta power in risky decision making remain unclear. The first aim of the present study was to replicate the earlier found relationship and examine the specific contributions of theta and beta power in risky decision making using the Iowa Gambling Task. The second aim of the study was to examine whether the relation were associated with differences in reward or punishment sensitivity. We replicated the earlier found relationship by showing a positive association between theta/beta ratio and risky decision making. This correlation was mainly driven by theta oscillations. Furthermore, theta power correlated with reward motivated learning, but not with punishment learning. The present results replicate and extend earlier findings by providing novel insights into the relation between thetabeta ratios and risky decision making. Specifically, findings show that resting-state theta activity is correlated with reinforcement learning, and that this association may be explained by differences in reward sensitivity.

  18. Substrate-bound outward-open state of the betaine transporter BetP provides insights into Na+ coupling

    Science.gov (United States)

    Perez, Camilo; Faust, Belinda; Mehdipour, Ahmad Reza; Francesconi, Kevin A.; Forrest, Lucy R.; Ziegler, Christine

    2014-07-01

    The Na+-coupled betaine symporter BetP shares a highly conserved fold with other sequence unrelated secondary transporters, for example, with neurotransmitter symporters. Recently, we obtained atomic structures of BetP in distinct conformational states, which elucidated parts of its alternating-access mechanism. Here, we report a structure of BetP in a new outward-open state in complex with an anomalous scattering substrate, adding a fundamental piece to an unprecedented set of structural snapshots for a secondary transporter. In combination with molecular dynamics simulations these structural data highlight important features of the sequential formation of the substrate and sodium-binding sites, in which coordinating water molecules play a crucial role. We observe a strictly interdependent binding of betaine and sodium ions during the coupling process. All three sites undergo progressive reshaping and dehydration during the alternating-access cycle, with the most optimal coordination of all substrates found in the closed state.

  19. Theoretical insight into the excited-state intramolecular proton transfer mechanisms of three amino-type hydrogen-bonding molecules

    Science.gov (United States)

    An, Beibei; Yuan, Huijuan; Zhu, Qiuling; Li, Yuanyuan; Guo, Xugeng; Zhang, Jinglai

    2017-03-01

    Excited-state intramolecular proton transfer (ESIPT) dynamics of the amino-type hydrogen-bonding compound 2-(2‧-aminophenyl)benzothiazole (PBT-NH2) as well as its two derivatives 2-(5‧-cyano-2‧-aminophenyl)benzothiazole (CN-PBT-NH2) and 2-(5‧-cyano-2‧-tosylaminophenyl)benzothiazole (CN-PBT-NHTs) were studied by the time-dependent density functional theory (TD-DFT) approach with the B3LYP density functional, and their absorption and emission spectra were also explored at the same level of theory. A good agreement is observed between the theoretical simulations and experimental spectra, indicating that the present calculations are reasonably reliable. In addition, it is also found that the energy barriers of the first excited singlet state of the three targeted molecules along the ESIPT reaction are computed to be 0.38, 0.34 and 0.12 eV, respectively, showing the trend of gradual decrease, which implies that the introduction of the electron-withdrawing cyano or tosyl group can facilitate the occurrence of the ESIPT reaction of these amino-type H-bonding systems. Following the ESIPT, both CN-PBT-NH2 and CN-PBT-NHTs dye molecules can undergo the cis-trans isomerization reactions in the ground-state and excited-state potential energy curves along the C2-C3 bond between benzothiazole and phenyl moieties, where the energy barriers of the trans-tautomer → cis-tautomer isomerizations in the ground states are calculated to be 0.83 and 0.34 eV, respectively. According to our calculations, it is plausible that there may exist the long-lived trans-tautomer species in the ground states of CN-PBT-NH2 and CN-PBT-NHTs.

  20. Metabolomic Profiling in Selaginella lepidophylla at Various Hydration States Provides New Insights into the Mechanistic Basis of Desiccation Tolerance

    Institute of Scientific and Technical Information of China (English)

    Abou Yobi; Bernard W.M.Wone; Wenxin Xu; Danny C.Alexander; Lining Guo; John A.Ryals; Melvin J.Oliver

    2013-01-01

    Selaginella lepidophylla is one of only a few species of spike mosses (Selaginellaceae) that have evolved desiccation tolerance (DT) or the ability to 'resurrect' from an air-dried state.In order to understand the metabolic basis of DT,S.lepidophylla was subjected to a five-stage,rehydration/dehydration cycle,then analyzed using non-biased,global metabolomics profiling technology based on GC/MS and UHLC/MS/MS2 platforms.A total of 251 metabolites including 167 named (66.5%) and 84 (33.4%) unnamed compounds were characterized.Only 42 (16.7%) and 74 (29.5%) of compounds showed significantly increased or decreased abundance,respectively,indicating that most compounds were produced constitutively,including highly abundant trehalose,sucrose,and glucose.Several glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle intermediates showed increased abundance at 100% relative water content (RWC) and 50% RWC.Vanillate,a potent antioxidant,was also more abundant in the hydrated state.Many different sugar alcohols and sugar acids were more abundant in the hydrated state.These polyols likely decelerate the rate of water loss during the drying process as well as slow water absorption during rehydration,stabilize proteins,and scavenge reactive oxygen species (ROS).In contrast,nitrogen-rich and γ-glutamyl amino acids,citrulline,and nucleotide catabolism products (e.g.allantoin) were more abundant in the dry states,suggesting that these compounds might play important roles in nitrogen remobilization during rehydration or in ROS scavenging.UV-protective compounds such as 3-(3-hydroxyphenyl)propionate,apigenin,and naringenin,were more abundant in the dry states.Most lipids were produced constitutively,with the exception of choline phosphate,which was more abundant in dry states and likely plays a role in membrane hydration and stabilization.In contrast,several polyunsaturated fatty acids were more abundant in the hydrated states,suggesting that these compounds

  1. Hospital care and capacity in the tri-state region of Indiana, Kentucky, and Ohio: analysis and insights.

    Science.gov (United States)

    Burns, David J; Chinta, Ravi; Kashyap, Vishal; Manolis, Chris; Sen, Amit

    2008-01-01

    Hospitals are a significant part of the burgeoning healthcare sector in the United States (U.S.) economy. Despite the availability of what some describe as the world's best healthcare, the U.S. suffers from wide discrepancies in healthcare provision across hospitals and regions of the country. Specifically, capacity, utilization, quality, and even financial performance of hospitals vary widely. Based on secondary data from 533 hospitals in the adjoining states of Indiana, Kentucky, and Ohio, this study develops several comparative metrics that enable benchmarking, which, in turn, leads to several inferences and implications for hospital administrators. The paper concludes with implications for hospital administrators and suggestions for future research.

  2. Metabolomic profiling in Selaginella lepidophylla at various hydration states provides new insights into the mechanistic basis of desiccation tolerance.

    Science.gov (United States)

    Yobi, Abou; Wone, Bernard W M; Xu, Wenxin; Alexander, Danny C; Guo, Lining; Ryals, John A; Oliver, Melvin J; Cushman, John C

    2013-03-01

    Selaginella lepidophylla is one of only a few species of spike mosses (Selaginellaceae) that have evolved desiccation tolerance (DT) or the ability to 'resurrect' from an air-dried state. In order to understand the metabolic basis of DT, S. lepidophylla was subjected to a five-stage, rehydration/dehydration cycle, then analyzed using non-biased, global metabolomics profiling technology based on GC/MS and UHLC/MS/MS(2) platforms. A total of 251 metabolites including 167 named (66.5%) and 84 (33.4%) unnamed compounds were characterized. Only 42 (16.7%) and 74 (29.5%) of compounds showed significantly increased or decreased abundance, respectively, indicating that most compounds were produced constitutively, including highly abundant trehalose, sucrose, and glucose. Several glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle intermediates showed increased abundance at 100% relative water content (RWC) and 50% RWC. Vanillate, a potent antioxidant, was also more abundant in the hydrated state. Many different sugar alcohols and sugar acids were more abundant in the hydrated state. These polyols likely decelerate the rate of water loss during the drying process as well as slow water absorption during rehydration, stabilize proteins, and scavenge reactive oxygen species (ROS). In contrast, nitrogen-rich and γ-glutamyl amino acids, citrulline, and nucleotide catabolism products (e.g. allantoin) were more abundant in the dry states, suggesting that these compounds might play important roles in nitrogen remobilization during rehydration or in ROS scavenging. UV-protective compounds such as 3-(3-hydroxyphenyl)propionate, apigenin, and naringenin, were more abundant in the dry states. Most lipids were produced constitutively, with the exception of choline phosphate, which was more abundant in dry states and likely plays a role in membrane hydration and stabilization. In contrast, several polyunsaturated fatty acids were more abundant in the hydrated states

  3. New insights into mutable collagenous tissue: correlations between the microstructure and mechanical state of a sea-urchin ligament.

    Directory of Open Access Journals (Sweden)

    Ana R Ribeiro

    Full Text Available The mutable collagenous tissue (MCT of echinoderms has the ability to undergo rapid and reversible changes in passive mechanical properties that are initiated and modulated by the nervous system. Since the mechanism of MCT mutability is poorly understood, the aim of this work was to provide a detailed morphological analysis of a typical mutable collagenous structure in its different mechanical states. The model studied was the compass depressor ligament (CDL of a sea urchin (Paracentrotus lividus, which was characterized in different functional states mimicking MCT mutability. Transmission electron microscopy, histochemistry, cryo-scanning electron microscopy, focused ion beam/scanning electron microscopy, and field emission gun-environmental scanning electron microscopy were used to visualize CDLs at the micro- and nano-scales. This investigation has revealed previously unreported differences in both extracellular and cellular constituents, expanding the current knowledge of the relationship between the organization of the CDL and its mechanical state. Scanning electron microscopies in particular provided a three-dimensional overview of CDL architecture at the micro- and nano-scales, and clarified the micro-organization of the ECM components that are involved in mutability. Further evidence that the juxtaligamental cells are the effectors of these changes in mechanical properties was provided by a correlation between their cytology and the tensile state of the CDLs.

  4. The Effect of Cellulose Crystal Structure and Solid-State Morphology on the Activity of Cellulases

    Energy Technology Data Exchange (ETDEWEB)

    Stipanovic, Arthur J [SUNY College of Environmental Science and Forestry

    2014-11-17

    Consistent with the US-DOE and USDA “Roadmap” objective of producing ethanol and chemicals from cellulosic feedstocks more efficiently, a three year research project entitled “The Effect of Cellulose Crystal Structure and Solid-State Morphology on the Activity of Cellulases” was initiated in early 2003 under DOE sponsorship (Project Number DE-FG02-02ER15356). A three year continuation was awarded in June 2005 for the period September 15, 2005 through September 14, 2008. The original goal of this project was to determine the effect of cellulose crystal structure, including allomorphic crystalline form (Cellulose I, II, III, IV and sub-allomorphs), relative degree of crystallinity and crystallite size, on the activity of different types of genetically engineered cellulase enzymes to provide insight into the mechanism and kinetics of cellulose digestion by “pure” enzymes rather than complex mixtures. We expected that such information would ultimately help enhance the accessibility of cellulose to enzymatic conversion processes thereby creating a more cost-effective commercial process yielding sugars for fermentation into ethanol and other chemical products. Perhaps the most significant finding of the initial project phase was that conversion of native bacterial cellulose (Cellulose I; BC-I) to the Cellulose II (BC-II) crystal form by aqueous NaOH “pretreatment” provided an increase in cellulase conversion rate approaching 2-4 fold depending on enzyme concentration and temperature, even when initial % crystallinity values were similar for both allomorphs.

  5. An active state of the BL Lac Object Markarian 421 detected by INTEGRAL in April 2013

    CERN Document Server

    Pian, E; Fiocchi, M; Bazzano, A; Foschini, L; Tavecchio, F; Bianchin, V; Boissay, R; Castignani, G; Ferrigno, C; Raiteri, C M; Villata, M; Beckmann, V; D'Ammando, F; Hudec, R; Malaguti, G; Maraschi, L; Pursimo, T; Romano, P; Soldi, S; Stamerra, A; Treves, A; Ubertini, P; Vercellone, S; Walter, R

    2013-01-01

    (abridged) Multi-wavelength variability of blazars offers effective insight into the mechanisms through which energy is propagated from the center down the jet. In this context, we activated INTEGRAL observations of the blazar Markarian 421 in an active state on 16-21 April 2013, and complemented them with Fermi-LAT data. We obtained well sampled optical, soft and hard X-ray light curves that show the presence of two flares, the first one reaching a brighter maximum than the second one at X-rays. The average flux in the 20-100 keV range is 9.1e-11 cgs and the nuclear average apparent magnitude, corrected for Galactic extinction, is V ~ 12.2. In the time-resolved JEMX+IBIS spectra we see a change of spectral slope at an energy that correlates with flux, as expected in refreshed energy injections in a population of electrons that cool thereafter via synchrotron radiation. During the observation, the variability level increases monotonically from the optical to the hard X-rays, and the cross-correlation analysis...

  6. Bidirectional modulation of substantia nigra activity by motivational state.

    Directory of Open Access Journals (Sweden)

    Mark A Rossi

    Full Text Available A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra.

  7. Insight on the energy in the United States; Apercus sur l'energie aux Etats-Unis

    Energy Technology Data Exchange (ETDEWEB)

    Jamet, Ph

    2006-11-15

    This document recapitulates the main characteristics and the key data of the energy in the United States (fossil energies, renewable energies, electric power production). The main american strategies are then described as the actions at the international scale during the last five years. The main data of the research programs in the energy domain are presented and the possible consequences of the government change at the Congress are analyzed. (A.L.B.)

  8. Diverse activation states of RhoA in human lung cancer cells: contribution of G protein coupled receptors.

    Science.gov (United States)

    Touge, Hirokazu; Chikumi, Hiroki; Igishi, Tadashi; Kurai, Jun; Makino, Haruhiko; Tamura, Yoshisato; Takata, Miyako; Yoneda, Kazuhiko; Nakamoto, Masaki; Suyama, Hisashi; Gutkind, J Silvio; Shimizu, Eiji

    2007-03-01

    Rho GTPases play an essential role in the control of various cellular functions. Accumulating evidence suggests that RhoA overexpression contributes to human cancer development. However, the activation states of RhoA are poorly defined in cancer cells. In this study, we examined both the expression levels and the activation states of RhoA in various lung cancer cells by quantitative real-time reverse transcriptase-polymerase chain reaction and in vivo Rho guanine nucleotide exchange assay, respectively. Moreover, we dissected the signaling pathway from the cell surface receptors to RhoA using a broad-spectrum G protein coupled receptor (GPCR) antagonist, [D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP), and a recently reported Galphaq/11-selective inhibitor, YM-254890. We found that RhoA was expressed highly in large cell carcinoma cells but only weakly in adenocarcinoma cells. The activation states of RhoA are considerably different from its expression profiles. We found that four of six small cell lung carcinoma (SCLC) cell lines exhibited a moderate to high activation rate of RhoA. The addition of [D-Arg1,D-Trp5,7,9,Leu11]SP reduced RhoA activity by almost 60% in H69 SCLC cells. The addition of YM-254890 had no effect on RhoA activity in H69 cells. Our results suggest that RhoA is activated in various lung cancer cells independent of its expression levels, and the high activation state of RhoA in SCLC cells mainly depends on a neuroendocrine peptide autocrine system which signals through Galpha12 coupled GPCR to RhoA. This study provides new insights into RhoA signaling in lung cancer cells and may help in developing novel therapeutic strategies against lung cancer.

  9. GG high accuracy test of the equivalence principle: state of the art, laboratory prototype and new insights

    Science.gov (United States)

    Nobili, Anna M.; Pegna, Raffaello; Comandi, Gian Luca; Bramanti, Donato; Anselmi, Alberto; Catastini, Giuseppe

    The GG ("Galileo Galilei") satellite experiment aims to test the Equivalence Principle (EP) to 10-17 , an extremely ambitious goal (due to improve current best results by 4 orders of magnitude) that should tell us in a clear cut way whether we are in the presence of a new long-range physical interaction (violation) or not (confirmation). Either way, it would be a major result. An end-to-end space experiment simulator was constructed at TAS-I based on GOCE simulator and ASI (Agenzia Spaziale Italiana) funding. The resulting error budget is consistent with the mission goal, which can be realized in 4 years from the start of Phase B. In the lab, a full scale prototype has provided a 25 days continuous run with a sensitivity -in the field of the Sun, hence at diurnal frequency- of a few nanometers in the relative displacement of the proof masses, to be compared with the picometer level required in space for GG to achieve its goal. A passive suspended prototype is under completion in order to reduce ground platform noise by means of an appropriate cardanic suspension which has now been proved to be able to reduce diurnal terrain noise by a factor 104 . The crucial issue of thermal noise has been recently revisited and a major new insight has come thanks to M. Shao (JPL): in GG, by up-converting the frequency of an EP violation signal in the field of the Earth from its (low) orbital frequency of 1.7 · 10-4 Hz to the (high) rotation/modulation frequency of 1Hz -the highest ever in EP experiments- proof mass thermal noise is reduced by orders of magnitude, as the ratio of these frequencies squared. Instead, cooling the experiment to superfluid He temperature would only reduce thermal noise by a factor 10. This is a feature unique to GG. It now appears that, if equipped with an intrinsic differential transducer such as a SIM like laser gauge, GG may indeed aim to an EP test to 10-18 . The end-to-end GG simulator built at TAS-I in 2009 during GG Phase A-2 study is the

  10. Functional imaging reveals movement preparatory activity in the vegetative state

    Directory of Open Access Journals (Sweden)

    Tristan A Bekinschtein

    2011-01-01

    Full Text Available The Vegetative State (VS is characterized by the absence of awareness of self or the environment and preserved autonomic functions. The diagnosis relies critically on the lack of consistent signs of purposeful behavior in response to external stimulation. Yet, given that patients with disorders of consciousness often exhibit fragmented movement patterns, voluntary actions may go unnoticed. Here we designed a simple motor paradigm that could potentially detect residual conscious awareness in VS patients with mild to severe brain damage by examining the neural correlates of motor preparation in response to verbal commands. Twenty-four patients who met the diagnostic criteria for VS were recruited for this study. Eleven of these patients showing preserved auditory evoked potentials underwent functional magnetic resonance imaging (fMRI to test for basic speech processing. Five of these patients, who showed word related activity, were included in a second fMRI study aimed at detecting functional changes in premotor cortex elicited by specific verbal instructions to move either their left or their right hand. Despite the lack of overt muscle activity, two patients out of five activated the dorsal premotor cortex contralateral to the instructed hand, consistent with movement preparation. Given that movement preparation in response to a motor command is a sign of purposeful behavior, our results are consistent with residual conscious awareness in these patients. We believe that the identification of positive results with fMRI using this simple task, may complement the clinical assessment by helping attain a more precise diagnosis in patients with disorders of consciousness.

  11. Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

    Science.gov (United States)

    Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

    2016-03-27

    In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK.

  12. The Effect of Detergent, Temperature, and Lipid on the Oligomeric State of MscL Constructs: Insights from Mass Spectrometry.

    Science.gov (United States)

    Reading, Eamonn; Walton, Troy A; Liko, Idlir; Marty, Michael T; Laganowsky, Arthur; Rees, Douglas C; Robinson, Carol V

    2015-05-21

    The mechanosensitive channel of large conductance (MscL) acts as an emergency release valve for osmotic shock of bacteria preventing cell lysis. The large pore size, essential for function, requires the formation of oligomers with tetramers, pentamers, or hexamers observed depending on the species and experimental approach. We applied non-denaturing (native) mass spectrometry to five different homologs of MscL to determine the oligomeric state under more than 50 different experimental conditions elucidating lipid binding and subunit stoichiometry. We found equilibrium between pentameric and tetrameric species, which can be altered by detergent, disrupted by binding specific lipids, and perturbed by increasing temperature (37°C). We also established the presence of lipopolysaccharide bound to MscL and other membrane proteins expressed in Escherichia coli, revealing a potential source of heterogeneity. More generally, we highlight the use of mass spectrometry in probing membrane proteins under a variety of detergent-lipid environments relevant to structural biology.

  13. Comparison of solid-state dipolar couplings and solution relaxation data provides insight into protein backbone dynamics.

    Science.gov (United States)

    Chevelkov, Veniamin; Xue, Yi; Linser, Rasmus; Skrynnikov, Nikolai R; Reif, Bernd

    2010-04-14

    Analyses of solution (15)N relaxation data and solid-state (1)H(N)-(15)N dipolar couplings from a small globular protein, alpha-spectrin SH3 domain, produce a surprisingly similar pattern of order parameters. This result suggests that there is little or no ns-mus dynamics throughout most of the sequence and, in particular, in the structured portion of the backbone. At the same time, evidence of ns-mus motions is found in the flexible loops and termini. These findings, corroborated by the MD simulations of alpha-spectrin SH3 in a hydrated crystalline environment and in solution, are consistent with the picture of protein dynamics that has recently emerged from the solution studies employing residual dipolar couplings.

  14. Estimability of recharge through groundwater model calibration: Insights from a field-scale steady-state example

    Science.gov (United States)

    Knowling, Matthew J.; Werner, Adrian D.

    2016-09-01

    The ability of groundwater models to inform recharge through calibration is hampered by the correlation between recharge and aquifer parameters such as hydraulic conductivity (K), and the insufficient information content of observation datasets. These factors collectively result in non-uniqueness of parameter estimates. Previous studies that jointly estimate spatially distributed recharge and hydraulic parameters are limited to synthetic test cases and/or do not evaluate the effect of non-uniqueness. The extent to which recharge can be informed by calibration is largely unknown for practical situations, in which complexities such as parameter heterogeneities are inherent. In this study, a systematic investigation of recharge, inferred through model calibration, is undertaken using a series of numerical experiments that include varying degrees of hydraulic parameter information. The analysis involves the use of a synthetic reality, based on a regional-scale, highly parameterised, steady-state groundwater model of Uley South Basin, South Australia. Parameter identifiability is assessed to evaluate the ability of parameters to be estimated uniquely. Results show that a reasonable inference of recharge (average recharge error 100 K values across the 129 km2 study area). The introduction of pumping data into the calibration reduces error in both the average recharge and its spatial variability, whereas submarine groundwater discharge (as a calibration target) reduces average recharge error only. Nonetheless, the estimation of steady-state recharge through inverse modelling may be impractical for real-world settings, limited by the need for unrealistic amounts of hydraulic parameter and groundwater level data. This study provides a useful benchmark for evaluating the extent to which field-scale groundwater models can be used to inform recharge subject to practical data-availability limitations.

  15. Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

    Directory of Open Access Journals (Sweden)

    C Devin Brisson

    Full Text Available Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT imaging in response to 10 minutes of oxygen/glucose deprivation (OGD revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival

  16. Steel passive state stability in activated fly ash mortars

    Directory of Open Access Journals (Sweden)

    Fernández-Jiménez, A.

    2010-12-01

    Full Text Available The present study explores the behaviour of structural steel embedded in Portland cement (OPC mortars and NaOH- and NaOH-waterglass-activated fly ash, in the presence and absence of 2 % Cl- (CaCl2. Variations were determined in the corrosion potential (Ecorr, linear polarization resistance (Rp and corrosion current density (icorr under different environmental conditions (90 days at 95 % relative humidity (RH, 30 days at ≈ 30 % RH, 760 days at ≈ 95 % RH. In the absence of Cl-, fly ash mortars were able to passivate steel reinforcement, although the stability of the passive state in changing environmental conditions was found to depend heavily on the activating solution used. Steel corrosion in the presence of 2 % Cl- was observed to be similar to the corrosion reported for the material in OPC mortars.

    En el presente trabajo se estudia el comportamiento del acero estructural embebido en morteros de cemento Pórtland (OPC y de cenizas volantes activadas con NaOH y una mezcla de NaOH y waterglass, en ausencia y en presencia de un 2% de Cl- (CaCl2. Se determino la evolución del potencial de corrosión (Ecorr, la resistencia de polarización lineal (Rp y la intensidad de corrosión (icorr, variando las condiciones ambientales (90 días al 95% de humedad relativa (HR-30 días a ≈ 30% HR- 760 días a ≈ 95% HR. En ausencia de Cl- los morteros de cenizas volantes activadas pueden pasivar los refuerzos de acero, si bien la estabilidad del estado pasivo ante cambios en las condiciones ambientales parece mostrar una fuerte dependencia de la solución activadora empleada. En presencia de un 2% de Cl- los aceros se corroen mostrando en comportamiento similar al observado en morteros en base OPC.

  17. A GTPase chimera illustrates an uncoupled nucleotide affinity and release rate, Providing insight into the activation mechanism

    DEFF Research Database (Denmark)

    Guilfoyle, Amy P.; Deshpande, Chandrika N.; Font Sadurni, Josep;

    2014-01-01

    The release of GDP from GTPases signals the initiation of a GTPase cycle, where the association of GTP triggers conformational changes promoting binding of downstream effector molecules. Studies have implicated the nucleotide-binding G5 loop to be involved in the GDP release mechanism. For example......, biophysical studies on both the eukaryotic Gα proteins and the GTPase domain (NFeoB) of prokaryotic FeoB proteins have revealed conformational changes in the G5 loop that accompany nucleotide binding and release. However, it is unclear whether this conformational change in the G5 loop is a prerequisite...... GTPase activity at a similar level to wild-type NFeoB, and structural analyses of the nucleotide-free and GDP-bound proteins show that the G5 loop adopts conformations analogous to that of the human nucleotide-bound Giα1 protein in both states. Interestingly, isothermal titration calorimetry and stopped...

  18. The local physical structure of amorphous hydrogenated boron carbide: insights from magic angle spinning solid-state NMR spectroscopy.

    Science.gov (United States)

    Paquette, Michelle M; Li, Wenjing; Sky Driver, M; Karki, Sudarshan; Caruso, A N; Oyler, Nathan A

    2011-11-01

    Magic angle spinning solid-state nuclear magnetic resonance spectroscopy techniques are applied to the elucidation of the local physical structure of an intermediate product in the plasma-enhanced chemical vapour deposition of thin-film amorphous hydrogenated boron carbide (B(x)C:H(y)) from an orthocarborane precursor. Experimental chemical shifts are compared with theoretical shift predictions from ab initio calculations of model molecular compounds to assign atomic chemical environments, while Lee-Goldburg cross-polarization and heteronuclear recoupling experiments are used to confirm atomic connectivities. A model for the B(x)C:H(y) intermediate is proposed wherein the solid is dominated by predominantly hydrogenated carborane icosahedra that are lightly cross-linked via nonhydrogenated intraicosahedral B atoms, either directly through B-B bonds or through extraicosahedral hydrocarbon chains. While there is no clear evidence for extraicosahedral B aside from boron oxides, ∼40% of the C is found to exist as extraicosahedral hydrocarbon species that are intimately bound within the icosahedral network rather than in segregated phases.

  19. 20 CFR 631.41 - Allowable State activities.

    Science.gov (United States)

    2010-04-01

    ...) States may use funds reserved under § 631.32(c) of this part, subject to the provisions of the State... than basic and remedial education, literacy and English for non-English speakers training,...

  20. Aeroelastic code development activities in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Wright, A.D. [National Renewable Energy Lab., Golden, Colorado (United States)

    1996-09-01

    Designing wind turbines to be fatigue resistant and to have long lifetimes at minimal cost is a major goal of the federal wind program and the wind industry in the United States. To achieve this goal, we must be able to predict critical loads for a wide variety of different wind turbines operating under extreme conditions. The codes used for wind turbine dynamic analysis must be able to analyze a wide range of different wind turbine configurations as well as rapidly predict the loads due to turbulent wind inflow with a minimal set of degrees of freedom. Code development activities in the US have taken a two-pronged approach in order to satisfy both of these criteria: (1) development of a multi-purpose code which can be used to analyze a wide variety of wind turbine configurations without having to develop new equations of motion with each configuration change, and (2) development of specialized codes with minimal sets of specific degrees of freedom for analysis of two- and three-bladed horizontal axis wind turbines and calculation of machine loads due to turbulent inflow. In the first method we have adapted a commercial multi-body dynamics simulation package for wind turbine analysis. In the second approach we are developing specialized codes with limited degrees of freedom, usually specified in the modal domain. This paper will summarize progress to date in the development, validation, and application of these codes. (au) 13 refs.

  1. Physiological state of life in the buried biosphere: insights from amino acid racemization modeling and superresolution microscopy

    DEFF Research Database (Denmark)

    Braun, Stefan

    2016-01-01

    in the deep seabed are less abundant (cells cm^−3) and metabolize at the lowest rates reported for life on Earth. The persisting organ- isms in the deep seabed have to efficiently use the sparse amount of available energy to repair cell damage, maintain viability, and ultimately grow. Cell...... that is up to four times lower than pre- vious estimates. For example, the cellular carbon content was 19-31 fg C cell^−1, which is at the lower end of previous estimations and will influence global estimates of microbial biomass and activity. Measurements of the body size of sub-seafloor microbial cells......, the number of cells per volume of sediment is generally very high (∼10^9 cells cm^−3 sediment). A steep decline in nutrient and energy availability with depth in the seabed, however, poses a strong constraint on the community size and metabolic rate of subsurface microorganisms. Consequently, cells...

  2. INFLUENCE OF BIOLOGICALLY ACTIVE AGENTS ON A STRUCTURAL STATE AND THE ENZYMATIC ACTIVITY OF BLACK ORDINARY CARBONATED SOIL

    Directory of Open Access Journals (Sweden)

    Lychman V. A.

    2014-04-01

    Full Text Available The results of a long-term research of the influence of various biologically active agents (a humic preparation Lignogumat and microbiological Baikal EM fertilizer on a structural state and the enzymatic activity of ordinary carbonated black soil are presented. It has been established that biologically active substances contribute to increased enzymatic activity, humus and improve the soil structure

  3. The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

    NARCIS (Netherlands)

    Bosma, I.; Stam, C.; Douw, L.; Bartolomei, F.; Heimans, J.; Dijk, van B.; Postma, T.; Klein, M.; Reijneveld, J.

    2008-01-01

    Purpose: In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activ

  4. The influence of low-grade glioma on resting state oscillatory brain activity : a magnetoencephalography study

    NARCIS (Netherlands)

    Bosma, I; Stam, C J; Douw, L; Bartolomei, F; Heimans, J J; van Dijk, B W; Postma, T J; Klein, M; Reijneveld, J C

    2008-01-01

    PURPOSE: In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activ

  5. State support as factor of increase of innovative activity of industrial enterprises

    Directory of Open Access Journals (Sweden)

    N.N. Bondarenko

    2011-10-01

    Full Text Available The article is devoted research of factors of increase of innovative activity of enterprise, the indexes of innovative activity of industrial enterprises are analysed in Ukraine, the necessity of creation of attractive terms is grounded for development of innovative activity and increase of innovative activity of management subjects at state level, the forms of state support as factor of increase of innovative activity of industrial enterprises are considered.

  6. More Active Living-oriented County and Municipal Zoning is Associated with Increased Adult Leisure Time Physical Activity-United States, 2011.

    Science.gov (United States)

    Chriqui, Jamie F; Nicholson, Lisa M; Thrun, Emily; Leider, Julien; Slater, Sandy J

    2016-01-01

    Although zoning is recognized for its role in facilitating healthy communities, no study has examined whether active living-oriented zoning codes are associated with adult leisure time physical activity (PA). This study sought to fill this gap and hypothesized that adult leisure time PA would be greater in communities with more progressive zoning code reforms and more active living-oriented zoning. Zoning codes for 1,617 county and municipal jurisdictions located in 30 states (covering ~40% of the U.S. population) were evaluated for code reform zoning and 11 active living markers. County-aggregated zoning measures were created for linking with five adult PA behaviors obtained from the 2011 Behavioral Risk Factor Surveillance System controlling for individual and county sociodemographics. Zoning elements most associated with adult PA included requirements for mixed use, active and passive recreation, bike parking/street furniture, and bike-pedestrian trails/paths. This study provides new insights as to the role that zoning can play in facilitating adult PA.

  7. Insight into the conformational stability of membrane-embedded BamA using a combined solution and solid-state NMR approach

    Energy Technology Data Exchange (ETDEWEB)

    Sinnige, Tessa; Houben, Klaartje [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Pritisanac, Iva [Physical and Theoretical Chemistry Laboratory (United Kingdom); Renault, Marie [Institute of Pharmacology and Structural Biology (France); Boelens, Rolf; Baldus, Marc, E-mail: m.baldus@uu.nl [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands)

    2015-04-15

    The β-barrel assembly machinery (BAM) is involved in folding and insertion of outer membrane proteins in Gram-negative bacteria, a process that is still poorly understood. With its 790 residues, BamA presents a challenge to current NMR methods. We utilized a “divide and conquer” approach in which we first obtained resonance assignments for BamA’s periplasmic POTRA domains 4 and 5 by solution NMR. Comparison of these assignments to solid-state NMR (ssNMR) data obtained on two BamA constructs including the transmembrane domain and one or two soluble POTRA domains suggested that the fold of POTRA domain 5 critically depends on the interface with POTRA 4. Using specific labeling schemes we furthermore obtained ssNMR resonance assignments for residues in the extracellular loop 6 that is known to be crucial for BamA-mediated substrate folding and insertion. Taken together, our data provide novel insights into the conformational stability of membrane-embedded, non-crystalline BamA.

  8. Consumer Insights

    Institute of Scientific and Technical Information of China (English)

    JANKOT

    2004-01-01

    Fang Jun, the head of consumer and market insights of Unilever Shanghai, has summarized his early life as a market in two sentences: rush about to study market changes;act all day to observe consumer behavior. And now?"Tell stories, conduct interviews and piece together different data; calculate numbers,build models and write reports."

  9. State Security Policy and Proxy Wars in Africa Ultima Ratio Regum 1 : Remix or Redux?; Strategic Insights, v. 9, issue 1 (Spring-Summer 2010) ; pp. 30-64.

    OpenAIRE

    2010-01-01

    This article appeared in Strategic Insights, v.9, issue 1 (Spring-Summer 2010) ; pp. 30-64. In this article, I am concerned with wartime alliances between states and armed nonstate actors, particularly in Africa. Heterogeneous military partnerships of this kind occur throughout the historical record. Louis XIV of France, whose aphorism about war and the state provides the title of this article, was an enthusiastic user of his enemies’ enemies; but so was Medieval England with its Viking ho...

  10. Altered baseline brain activity with 72 h of simulated microgravity--initial evidence from resting-state fMRI.

    Directory of Open Access Journals (Sweden)

    Yang Liao

    Full Text Available To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a -6° head down tilt (HDT. A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a -6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm(3 (13 voxels, which corresponded with the corrected threshold of P<0.05 determined by AlphaSim. Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment.

  11. State activities that promote fuel cell and hydrogen infrastructure development

    Energy Technology Data Exchange (ETDEWEB)

    Gangi, J. [Fuel Cells 2000, Washington, DC (United States). Breakthrough Technologies Inst.

    2007-07-01

    The fuel cell and hydrogen industry provide environmental benefits in addition to economic benefits in the form of jobs and business. This presentation outlined the initiatives, policy and partnerships that individual states are initiating to promote the commercialization of fuel cells and hydrogen fuels. Multi-state partnerships and regional organizations and initiatives were highlighted along with state programs, regulations, demonstrations and incentives that include hydrogen, fuel cells and zero emission vehicles. It was shown that 47 states and the District of Columbia (DC) are involved in the promotion of fuel cell or hydrogen legislation and funding. Breakthrough Technologies Institute, the parent organization of Fuel Cells 2000, and the U.S. Department of Energy's Hydrogen Program has launched a searchable database that catalogues all stationary installations, hydrogen fueling stations and vehicle demonstration programs in the United States, including cars, buses and specialty vehicles. The database is intended to be a guide for local, state and federal lawmakers to implement similar legislation and initiatives in their jurisdictions. The database includes regulations such as interconnection standards, renewable portfolio standards and net metering as well as legislation such as tax credits, grants, and loans. Roadmaps and funding/support for business incubators and relocation are included. The database is also an important tool for the general public who are trying to learn more about the technology. Although federal research money has mainly focused on transportation and related fuel technologies, individual states are targeting other applications and areas such as materials and components, stationary power and fuel storage.

  12. Large-Scale Brain Networks in Board Game Experts: Insights from a Domain-Related Task and Task-Free Resting State

    Science.gov (United States)

    Duan, Xujun; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Gao, Qing; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

    2012-01-01

    Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior. PMID:22427852

  13. Insights into induced earthquakes and aftershock activity with in-situ measurements of seismic velocity variations in an active underground mine

    Science.gov (United States)

    Brenguier, F.; Olivier, G.; Campillo, M.; Roux, P.; Shapiro, N.; Lynch, R.

    2015-12-01

    The behaviour of the crust shortly after large earthquakes has been the subject of numerous studies, but many co- and post-seismic processes remain poorly understood. Damage and healing of the bulk rock mass, post-seismic deformation and the mechanisms of earthquake triggering are still not well understood. These processes are important to properly model and understand the behaviour of faults and earthquake cycles.In this presentation, we will show how in-situ measurements of seismic velocity variations have given new insights into these co- and post-seismic processes. An experiment was performed where a blast was detonated in a tunnel in an underground mine, while seismic velocity variations were accurately (0.005 %) measured with ambient seismic noise correlations. Additionally, aftershock activity was examined and the influence of the removal of a piece of solid rock was estimated with elastic static stress modelling. The majority of the aftershocks were delayed with respect to the passing of the dynamic waves from the blast, while the locations of the aftershocks appeared clustered and not homogeneously spread around the blast location. A significant velocity drop is visible during the time of the blast, which is interpreted as co-seismic damage and plastic deformation. These non-elastic effects are healed by the confining stresses over a period of 5 days until the seismic velocity converges to a new baseline level. The instantaneous weakening and gradual healing observed from the velocity variations are qualitatively similar to results reported in laboratory studies. The change in the baseline level of the seismic velocity before and after the blast indicate a change in the static stress that is comparable to the results of elastic static stress modelling. The differences between the elastic model predictions and the seismic velocity variations could be due to zones of fractured rock, indicated by the spatial clustering of the aftershocks, that are not

  14. Novel Insights Into The Mode of Inhibition of Class A SHV-1 Beta-Lactamases Revealed by Boronic Acid Transition State Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    W Ke; J Sampson; C Ori; F Prati; S Drawz; C Bethel; R Bonomo; F van den Akker

    2011-12-31

    Boronic acid transition state inhibitors (BATSIs) are potent class A and C {beta}-lactamase inactivators and are of particular interest due to their reversible nature mimicking the transition state. Here, we present structural and kinetic data describing the inhibition of the SHV-1 {beta}-lactamase, a clinically important enzyme found in Klebsiella pneumoniae, by BATSI compounds possessing the R1 side chains of ceftazidime and cefoperazone and designed variants of the latter, compounds 1 and 2. The ceftazidime and cefoperazone BATSI compounds inhibit the SHV-1 {beta}-lactamase with micromolar affinity that is considerably weaker than their inhibition of other {beta}-lactamases. The solved crystal structures of these two BATSIs in complex with SHV-1 reveal a possible reason for SHV-1's relative resistance to inhibition, as the BATSIs adopt a deacylation transition state conformation compared to the usual acylation transition state conformation when complexed to other {beta}-lactamases. Active-site comparison suggests that these conformational differences might be attributed to a subtle shift of residue A237 in SHV-1. The ceftazidime BATSI structure revealed that the carboxyl-dimethyl moiety is positioned in SHV-1's carboxyl binding pocket. In contrast, the cefoperazone BATSI has its R1 group pointing away from the active site such that its phenol moiety moves residue Y105 from the active site via end-on stacking interactions. To work toward improving the affinity of the cefoperazone BATSI, we synthesized two variants in which either one or two extra carbons were added to the phenol linker. Both variants yielded improved affinity against SHV-1, possibly as a consequence of releasing the strain of its interaction with the unusual Y105 conformation.

  15. Student Activism in the High Schools of New York State.

    Science.gov (United States)

    Haake, Bernard F.; Langworthy, Philip B.

    The purpose of nine regional meetings between New York State Education Department personnel, educators and students from selected secondary school districts was to obtain information about unrest and the changing expectations of high school students. The following conclusions were made: (1) rising expectations of students are part of the "times,"…

  16. Solid-state fermentation: modelling fungal growth and activity.

    NARCIS (Netherlands)

    Smits, J.P.

    1998-01-01

    In solid-state fermentation (SSF) research, it is not possible to separate biomass quantitatively from the substrate. The evolution of biomass dry weight in time can therefore not be measured. Of the aiternatives to dry weight available, glucosamine content is most promising.Glucosamine is the monom

  17. 34 CFR 300.704 - State-level activities.

    Science.gov (United States)

    2010-07-01

    ... with disabilities, based on scientifically based research to improve educational instruction, in order to improve academic achievement to meet or exceed the objectives established by the State under..., and numeracy skills) in accordance with Part C of the Act to children with disabilities who...

  18. Resting-State Oscillatory Activity in Autism Spectrum Disorders

    Science.gov (United States)

    Cornew, Lauren; Roberts, Timothy P. L.; Blaskey, Lisa; Edgar, J. Christopher

    2012-01-01

    Neural oscillatory anomalies in autism spectrum disorders (ASD) suggest an excitatory/inhibitory imbalance; however, the nature and clinical relevance of these anomalies are unclear. Whole-cortex magnetoencephalography data were collected while 50 children (27 with ASD, 23 controls) underwent an eyes-closed resting-state exam. A Fast Fourier…

  19. Training Activity Summary Page (TASP) State and Tribe

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Training Activity Summary Page (formerly the Training Exit Survey Cover Page) dataset contains data about each training event. This dataset includes information...

  20. Some Directions in State Activities of Ye. F. Kankrin

    Directory of Open Access Journals (Sweden)

    Olga G. Larina

    2014-03-01

    Full Text Available The article studies biographical facts on Yegor Frantsevich Kankrin and contains an analysis of his activities in the office of Minister of Finance. Based on the archive, biographical and legislative sources, the article considers the system of measures taken by Kankrin in the financial, industrial, mining, wood industry and educational spheres. The authors studied his work at the Jewish (second Committee as well as the drawbacks in his professional activities and the reasons behind them.

  1. Tracking Sodium-Antimonide Phase Transformations in Sodium-Ion Anodes: Insights from Operando Pair Distribution Function Analysis and Solid-State NMR Spectroscopy.

    Science.gov (United States)

    Allan, Phoebe K; Griffin, John M; Darwiche, Ali; Borkiewicz, Olaf J; Wiaderek, Kamila M; Chapman, Karena W; Morris, Andrew J; Chupas, Peter J; Monconduit, Laure; Grey, Clare P

    2016-02-24

    Operando pair distribution function (PDF) analysis and ex situ (23)Na magic-angle spinning solid-state nuclear magnetic resonance (MAS ssNMR) spectroscopy are used to gain insight into the alloying mechanism of high-capacity antimony anodes for sodium-ion batteries. Subtraction of the PDF of crystalline NaxSb phases from the total PDF, an approach constrained by chemical phase information gained from (23)Na ssNMR in reference to relevant model compounds, identifies two previously uncharacterized intermediate species formed electrochemically; a-Na(3-x)Sb (x ≈ 0.4-0.5), a structure locally similar to crystalline Na3Sb (c-Na3Sb) but with significant numbers of sodium vacancies and a limited correlation length, and a-Na(1.7)Sb, a highly amorphous structure featuring some Sb-Sb bonding. The first sodiation breaks down the crystalline antimony to form first a-Na(3-x)Sb and, finally, crystalline Na3Sb. Desodiation results in the formation of an electrode formed of a composite of crystalline and amorphous antimony networks. We link the different reactivity of these networks to a series of sequential sodiation reactions manifesting as a cascade of processes observed in the electrochemical profile of subsequent cycles. The amorphous network reacts at higher voltages reforming a-Na(1.7)Sb, then a-Na(3-x)Sb, whereas lower potentials are required for the sodiation of crystalline antimony, which reacts to form a-Na(3-x)Sb without the formation of a-Na(1.7)Sb. a-Na(3-x)Sb is converted to crystalline Na3Sb at the end of the second discharge. We find no evidence of formation of NaSb. Variable temperature (23)Na NMR experiments reveal significant sodium mobility within c-Na3Sb; this is a possible contributing factor to the excellent rate performance of Sb anodes.

  2. National Study of State Universities and Land Grant Colleges: Off Campus Inservice Activities.

    Science.gov (United States)

    Seldin, Clement A.

    Information concerning off-campus inservice activity (OCIA) at state universities and land grant colleges in the United States was surveyed. There was a 92.5 percent response rate to questionnaires sent to 107 deans of schools, colleges, and departments of education. Inservice activities were considered to be courses, workshops, needs assessments,…

  3. 31 CFR 538.531 - Official activities of the United States Government and international organizations.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Official activities of the United States Government and international organizations. 538.531 Section 538.531 Money and Finance: Treasury....531 Official activities of the United States Government and international organizations. (a)...

  4. Measuring the performance of multi-agency programmatic permits for Washington State Department of Transportation activities

    OpenAIRE

    2005-01-01

    In 2001, the Washington State Legislature established the Transportation Permit Efficiency and Accountability Committee (TPEAC) to identify measures to streamline permit procedures for transportation activities and improve environmental outcomes. A programmatic subcommittee was created to develop a multi-agency approach for developing programmatic permits that would cover 60 to 70 percent of Washington State Department of Transportation (WSDOT) activities (mostly maintenance and preservation ...

  5. Models of Innovation Activity Firms and the Competitive State

    Directory of Open Access Journals (Sweden)

    Nekrasova Ekaterina, A.

    2015-12-01

    Full Text Available The paper clarified the concept of innovation activity of firms from the perspective of the model open innovation with traditional and alternative approaches to the methods of the protection of innovation activity results outlined. With the use of institutional tools, theoretical concepts and practical study the patterns of innovative activity of firms (external, internal & cooperative strategies are analyzed and the selection criteria for models of innovation are proposed on the basis of a comparison of transaction costs and benefits specific to the closed forms and conditions for cooperation. The forms of cooperation, their pros & cons are mentioned given the results of some empirical evidence. Practical recommendations for the Russian companies to organize their innovation activities are given, as well as on the improvement of competition policy with regard to the inclusion of innovation factor in the analysis of mergers in Russia (also based on the mechanism of the use of this factor by means of merger simulation models. The paper also suggests the criteria for the evaluation of collaborative R&D projects of firms as antitrust tools aimed to use the “rule of reason” when the decisions are made.

  6. Discussion on sea level fluctuations along the Adriatic coasts coupling to climate indices forced by solar activity: Insights into the future of Venice

    Science.gov (United States)

    Zanchettin, Davide; Traverso, Pietro; Tomasino, Mario

    2006-04-01

    The North Atlantic Oscillation (NAO), which is a dominant circulation pattern in Northern Hemisphere winter, is known to affect sea-level variability in the Mediterranean Sea mainly through the hydrostatic response of water masses to pressure anomalies and changes in evaporation/precipitation budgets. In this study the influence of the NAO on sea levels along the Adriatic coasts is re-assessed in the attempt to uncover the potential causes of the observed high sensitivity of the northern basin to NAO fluctuations. The investigation is focused on the role of the NAO as forcing factor of the winds blowing in the area and of the freshwaters input from the Po River, both of which influence the hydrodynamics of the Northern Adriatic. In addition, some insights into the future of Venice are discussed on the basis of the hypothesis that NAO phases are modulated by the varying solar activity through the intensity of the Earth's geomagnetic activity.

  7. Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors

    Directory of Open Access Journals (Sweden)

    Abdellah Messoussi

    2014-10-01

    Full Text Available Structural elucidation of the active (DFG-Asp in and inactive (DFG-Asp out states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

  8. Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes.

    Science.gov (United States)

    He, Dandan; Chiou, Jiachi; Zeng, Zhenling; Chan, Edward Wai-Chi; Liu, Jian-Hua; Chen, Sheng

    2016-10-01

    Clinical isolates producing hybrid CTX-M β-lactamases, presumably due to recombination between the blaCTX-M-15 and blaCTX-M-14 elements, have emerged in recent years. Among the hybrid enzymes, CTX-M-64 and CTX-M-14 display the most significant difference in catalytic activity. This study aims to investigate the mechanisms underlying such differential enzymatic activities in order to provide insight into the structure/function relationship of this class of enzymes. Sequence alignment analysis showed that the major differences between the amino acid composition of CTX-M-64 and CTX-M-14 lie at both the N and C termini of the enzymes. Single or multiple amino acid substitutions introduced into CTX-M-64 and CTX-M-14 were found to produce only minor effects on hydrolytic functions; such a finding is consistent with the notion that the discrepancy between the functional activities of the two enzymes is not the result of only a few amino acid changes but is attributable to interactions between a unique set of amino acid residues in each enzyme. This theory is supported by the results of the thermal stability assay, which confirmed that CTX-M-64 is significantly more stable than CTX-M-14. Our data confirmed that, in addition to the important residues located in the active site, residues distal to the active site also contribute to the catalytic activity of the enzyme through stabilizing its structural integrity.

  9. Monitoring and validating active site redox states in protein crystals.

    Science.gov (United States)

    Antonyuk, Svetlana V; Hough, Michael A

    2011-06-01

    High resolution protein crystallography using synchrotron radiation is one of the most powerful tools in modern biology. Improvements in resolution have arisen from the use of X-ray beamlines with higher brightness and flux and the development of advanced detectors. However, it is increasingly recognised that the benefits brought by these advances have an associated cost, namely deleterious effects of X-ray radiation on the sample (radiation damage). In particular, X-ray induced reduction and damage to redox centres has been shown to occur much more rapidly than other radiation damage effects, such as loss of resolution or damage to disulphide bridges. Selection of an appropriate combination of in-situ single crystal spectroscopies during crystallographic experiments, such as UV-visible absorption and X-ray absorption spectroscopy (XAFS), allows for effective monitoring of redox states in protein crystals in parallel with structure determination. Such approaches are also essential in cases where catalytic intermediate species are generated by exposure to the X-ray beam. In this article, we provide a number of examples in which multiple single crystal spectroscopies have been key to understanding the redox status of Fe and Cu centres in crystal structures. This article is part of a Special Issue entitled: Protein Structure and Function in the Crystalline State.

  10. Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.

    Science.gov (United States)

    Lemieux, Maxime; Chauvette, Sylvain; Timofeev, Igor

    2015-02-01

    During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state.

  11. United States-Russia: Environmental management activities, Summer 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    A Joint Coordinating Committee for Environmental Restoration and Waste Management (JCCEM) was formed between the US and Russia. This report describes the areas of research being studied under JCCEM, namely: Efficient separations; Contaminant transport and site characterization; Mixed wastes; High level waste tank remediation; Transuranic stabilization; Decontamination and decommissioning; and Emergency response. Other sections describe: Administrative framework for cooperation; Scientist exchange; Future actions; Non-JCCEM DOE-Russian activities; and JCCEM publications.

  12. What graph theory actually tells us about resting state interictal MEG epileptic activity.

    Science.gov (United States)

    Niso, Guiomar; Carrasco, Sira; Gudín, María; Maestú, Fernando; Del-Pozo, Francisco; Pereda, Ernesto

    2015-01-01

    Graph theory provides a useful framework to study functional brain networks from neuroimaging data. In epilepsy research, recent findings suggest that it offers unique insight into the fingerprints of this pathology on brain dynamics. Most studies hitherto have focused on seizure activity during focal epilepsy, but less is known about functional epileptic brain networks during interictal activity in frontal focal and generalized epilepsy. Besides, it is not clear yet which measures are most suitable to characterize these networks. To address these issues, we recorded magnetoencephalographic (MEG) data using two orthogonal planar gradiometers from 45 subjects from three groups (15 healthy controls (7 males, 24 ± 6 years), 15 frontal focal (8 male, 32 ± 16 years) and 15 generalized epileptic (6 male, 27 ± 7 years) patients) during interictal resting state with closed eyes. Then, we estimated the total and relative spectral power of the largest principal component of the gradiometers, and the degree of phase synchronization between each sensor site in the frequency range [0.5-40 Hz]. We further calculated a comprehensive battery of 15 graph-theoretic measures and used the affinity propagation clustering algorithm to elucidate the minimum set of them that fully describe these functional brain networks. The results show that differences in spectral power between the control and the other two groups have a distinctive pattern: generalized epilepsy presents higher total power for all frequencies except the alpha band over a widespread set of sensors; frontal focal epilepsy shows higher relative power in the beta band bilaterally in the fronto-central sensors. Moreover, all network indices can be clustered into three groups, whose exemplars are the global network efficiency, the eccentricity and the synchronizability. Again, the patterns of differences were clear: the brain network of the generalized epilepsy patients presented greater efficiency and lower

  13. What graph theory actually tells us about resting state interictal MEG epileptic activity

    Directory of Open Access Journals (Sweden)

    Guiomar Niso

    2015-01-01

    Full Text Available Graph theory provides a useful framework to study functional brain networks from neuroimaging data. In epilepsy research, recent findings suggest that it offers unique insight into the fingerprints of this pathology on brain dynamics. Most studies hitherto have focused on seizure activity during focal epilepsy, but less is known about functional epileptic brain networks during interictal activity in frontal focal and generalized epilepsy. Besides, it is not clear yet which measures are most suitable to characterize these networks. To address these issues, we recorded magnetoencephalographic (MEG data using two orthogonal planar gradiometers from 45 subjects from three groups (15 healthy controls (7 males, 24 ± 6 years, 15 frontal focal (8 male, 32 ± 16 years and 15 generalized epileptic (6 male, 27 ± 7 years patients during interictal resting state with closed eyes. Then, we estimated the total and relative spectral power of the largest principal component of the gradiometers, and the degree of phase synchronization between each sensor site in the frequency range [0.5–40 Hz]. We further calculated a comprehensive battery of 15 graph-theoretic measures and used the affinity propagation clustering algorithm to elucidate the minimum set of them that fully describe these functional brain networks. The results show that differences in spectral power between the control and the other two groups have a distinctive pattern: generalized epilepsy presents higher total power for all frequencies except the alpha band over a widespread set of sensors; frontal focal epilepsy shows higher relative power in the beta band bilaterally in the fronto-central sensors. Moreover, all network indices can be clustered into three groups, whose exemplars are the global network efficiency, the eccentricity and the synchronizability. Again, the patterns of differences were clear: the brain network of the generalized epilepsy patients presented greater

  14. A review of recent activity in the United States.

    Science.gov (United States)

    Cannon, H.L.; Petrie, W.L.

    1979-01-01

    Either an overabundance or a deficiency of trace metals in the food chain can ultimately affect adversely the health of livestock and man. Increasing interest in the United States in the distribution of metals in the environment and in metal pollutants has led to widespread interdisciplinary research sponsored by governmental, private and academic groups concerning the availability of trace elements for absorption by plants and animals, and the effects of trace elements throughout the food chain. Effects on the environment of coal-fired power plants, the mining and processing of metals, asbestos, and phosphate, and the disposal of industrial and nuclear wastes have also received much attention in the past few years.-Authors

  15. Predicting the activation states of the muscles governing upper esophageal sphincter relaxation and opening.

    Science.gov (United States)

    Omari, Taher I; Jones, Corinne A; Hammer, Michael J; Cock, Charles; Dinning, Philip; Wiklendt, Lukasz; Costa, Marcello; McCulloch, Timothy M

    2016-03-15

    The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these "mechanical states" of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of "activation state" maps may allow better physiological and pathophysiological interpretations of UES function.

  16. Insights into the dual activity of SIVmac239 Vif against human and African green monkey APOBEC3G.

    Directory of Open Access Journals (Sweden)

    Ritu Gaur

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 Vif is essential for viral evasion of the host antiviral protein APOBEC3G (APO3G. The Vif protein from a distantly related African green monkey (Agm simian immunodeficiency virus (SIVagm is unable to suppress the antiviral activity of human APO3G but is active against Agm APO3G. SIVmac Vif on the other hand, possesses antiviral activity against both human and Agm APO3G. In this study, we were interested in mapping domains in SIVmac Vif that are responsible for its dual activity against human and Agm APO3G. We constructed a series of Vif chimeras by swapping domains in SIVmac Vif with equivalent regions from SIVagm Vif and determined their activity against human and Agm APO3G. We found that replacing any region in SIVmac Vif by corresponding fragments from SIVagm Vif only moderately reduced the activity of the chimeras against Agm APO3G but in all cases resulted in a severe loss of activity against human APO3G. These results suggest that the domains in SIVmac Vif required for targeting human and Agm APO3G are distinct and cannot be defined as linear amino acid motifs but rather appear to depend on the overall structure of full-length SIVmac Vif.

  17. Viable But Not Culturable (VBNC) state of Brettanomyces bruxellensis in wine: New insights on molecular basis of VBNC behaviour using a transcriptomic approach.

    Science.gov (United States)

    Capozzi, Vittorio; Di Toro, Maria Rosaria; Grieco, Francesco; Michelotti, Vania; Salma, Mohammad; Lamontanara, Antonella; Russo, Pasquale; Orrù, Luigi; Alexandre, Hervé; Spano, Giuseppe

    2016-10-01

    The spoilage potential of Brettanomyces bruxellensis in wine is strongly connected with the aptitude of this yeast to enter in a Viable But Non Culturable (VBNC) state when exposed to the harsh wine conditions. In this work, we characterized the VBNC behaviour of seven strains of B. bruxellensis representing a regional intraspecific biodiversity, reporting conclusive evidence for the assessment of VBNC as a strain-dependent character. The VBNC behaviour was monitored by fluorescein diacetate staining/flow cytometry for eleven days after addition of 0.4, 0.6, 0.8, 1 and 1.2 mg/L of molecular SO2 (entrance in the VBNC state) and after SO2 removal (exit from the VBNC state). Furthermore, one representative strain was selected and RNA-seq analysis performed after exposure to 1.2 mg/L SO2 and during the recovery phase. 30 and 1634 genes were identified as differentially expressed following VBNC entrance and 'resuscitation', respectively. The results reported strongly suggested that the entrance in the SO2-induced VBNC state in B. bruxellensis is associated with both, sulfite toxicity and oxidative stress response, confirming the crucial role of genes/proteins involved in redox cell homeostasis. Among the genes induced during recovery, the expression of genes involved in carbohydrate metabolism and encoding heat shock proteins, as well as enriched categories including amino acid transport and transporter activity was observed. The evidences of a general repression of genes involved in DNA replication suggest the occurrence of a true resuscitation of cell rather than a simple regrowth.

  18. THE MODERN STATE OF ENTERPRISE INNOVATION ACTIVITY IN KAZAKHSTAN

    Directory of Open Access Journals (Sweden)

    Nurlan Kurmanov

    2015-09-01

    Full Text Available In the XXI century, the key to rapid socio-economic development is to have an effective innovation policy, aimed at introducing high "disruptive" technologies, new ways to organise and manage work, advanced inventions, and the means to progress scientific and technical achievements.The formation of an innovative economy in Kazakhstan is a complexity of economic, social, and political issues. An effective use of research findings and developments in the real economy is most important in terms of Kazakhstan’s successful competitiveness, assurance for high economic growth, improved quality of life, and to help realize other innovative priorities. In these circumstances, innovation management and development is becoming more relevant as the basis for developing Kazakh companies, by way of a defined set of relevant technical, operational, organizational, marketing, and financial operations.The purpose of this study is to identify characteristics and practical recommendations for the development and further improvement of management mechanisms relating to the innovative activity of enterprises in Kazakhstan. The study used a systematic approach of comparison, scientific abstraction, data collection, analysis and synthesis, applied expertise, and statistical methods. The core value of the work was to support the feasibility of a system for Kazakh enterprises to promote innovative activity and the development of high technologies.

  19. Crystal structure of a KSHV-SOX-DNA complex: insights into the molecular mechanisms underlying DNase activity and host shutoff.

    Science.gov (United States)

    Bagnéris, Claire; Briggs, Louise C; Savva, Renos; Ebrahimi, Bahram; Barrett, Tracey E

    2011-07-01

    The early lytic phase of Kaposi's sarcoma herpesvirus infection is characterized by viral replication and the global degradation (shutoff) of host mRNA. Key to both activities is the virally encoded alkaline exonuclease KSHV SOX. While the DNase activity of KSHV SOX is required for the resolution of viral genomic DNA as a precursor to encapsidation, its exact involvement in host shutoff remains to be determined. We present the first crystal structure of a KSHV SOX-DNA complex that has illuminated the catalytic mechanism underpinning both its endo and exonuclease activities. We further illustrate that KSHV SOX, similar to its Epstein-Barr virus homologue, has an intrinsic RNase activity in vitro that although an element of host shutoff, cannot solely account for the phenomenon.

  20. Insights into the phosphatase and the synthase activities of human bisphosphoglycerate mutase: a quantum mechanics/molecular mechanics simulation.

    Science.gov (United States)

    Chu, Wen-Ting; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2014-03-07

    Bisphosphoglycerate mutase (BPGM) is a multi-activity enzyme. Its main function is to synthesize the 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. This enzyme can also catalyze the 2,3-bisphosphoglycerate to the 3-phosphoglycerate. In this study, the reaction mechanisms of both the phosphatase and the synthase activities of human bisphosphoglycerate mutase were theoretically calculated by using the quantum mechanics/molecular mechanics method based on the metadynamics and umbrella sampling simulations. The simulation results not only show the free energy curve of the phosphatase and the synthase reactions, but also reveal the important role of some residues in the active site. Additionally, the energy barriers of the two reactions indicate that the activity of the synthase in human bisphosphoglycerate mutase is much higher than that of the phosphatase. The estimated reaction barriers are consistent with the experimental data. Therefore, our work can give important information to understand the catalytic mechanism of the bisphosphoglycerate mutase family.

  1. Tracking Sodium-Antimonide Phase Transformations in Sodium-Ion Anodes: Insights from Operando Pair Distribution Function Analysis and Solid-State NMR Spectroscopy

    Science.gov (United States)

    2016-01-01

    Operando pair distribution function (PDF) analysis and ex situ 23Na magic-angle spinning solid-state nuclear magnetic resonance (MAS ssNMR) spectroscopy are used to gain insight into the alloying mechanism of high-capacity antimony anodes for sodium-ion batteries. Subtraction of the PDF of crystalline NaxSb phases from the total PDF, an approach constrained by chemical phase information gained from 23Na ssNMR in reference to relevant model compounds, identifies two previously uncharacterized intermediate species formed electrochemically; a-Na3–xSb (x ≈ 0.4–0.5), a structure locally similar to crystalline Na3Sb (c-Na3Sb) but with significant numbers of sodium vacancies and a limited correlation length, and a-Na1.7Sb, a highly amorphous structure featuring some Sb–Sb bonding. The first sodiation breaks down the crystalline antimony to form first a-Na3–xSb and, finally, crystalline Na3Sb. Desodiation results in the formation of an electrode formed of a composite of crystalline and amorphous antimony networks. We link the different reactivity of these networks to a series of sequential sodiation reactions manifesting as a cascade of processes observed in the electrochemical profile of subsequent cycles. The amorphous network reacts at higher voltages reforming a-Na1.7Sb, then a-Na3–xSb, whereas lower potentials are required for the sodiation of crystalline antimony, which reacts to form a-Na3–xSb without the formation of a-Na1.7Sb. a-Na3–xSb is converted to crystalline Na3Sb at the end of the second discharge. We find no evidence of formation of NaSb. Variable temperature 23Na NMR experiments reveal significant sodium mobility within c-Na3Sb; this is a possible contributing factor to the excellent rate performance of Sb anodes. PMID:26824406

  2. Group III alcohol dehydrogenase from Pectobacterium atrosepticum: insights into enzymatic activity and organization of the metal ion-containing region.

    Science.gov (United States)

    Elleuche, Skander; Fodor, Krisztian; von der Heyde, Amélie; Klippel, Barbara; Wilmanns, Matthias; Antranikian, Garabed

    2014-05-01

    NAD(P)(+)-dependent alcohol dehydrogenases (ADH) are widely distributed in all phyla. These proteins can be assigned to three nonhomologous groups of isozymes, with group III being highly diverse with regards to catalytic activity and primary structure. Members of group III ADHs share a conserved stretch of amino acid residues important for cofactor binding and metal ion coordination, while sequence identities for complete proteins are highly diverse (90 %). A putative group III ADH PaYqhD has been identified in BLAST analysis from the plant pathogenic enterobacterium Pectobacterium atrosepticum. The PaYqhD gene was expressed in the heterologous host Escherichia coli, and the recombinant protein was purified in a two-step purification procedure to homogeneity indicating an obligate dimerization of monomers. Four conserved amino acid residues involved in metal ion coordination were substituted with alanine, and their importance for catalytic activity was confirmed by circular dichroism spectrum determination, in vitro, and growth experiments. PaYqhD exhibits optimal activity at 40 °C with short carbon chain aldehyde compounds and NADPH as cofactor indicating the enzyme to be an aldehyde reductase. No oxidative activities towards alcoholic compounds were detectable. EDTA completely inhibited catalytic activity and was fully restored by the addition of Co(2+). Activity measurements together with sequence alignments and structure analysis confirmed that PaYqhD belongs to the butanol dehydrogenase-like enzymes within group III of ADHs.

  3. Spectroscopic insights into the nature of active sites in iron–nitrogen–carbon electrocatalysts for oxygen reduction in acid

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Qingying; Ramaswamy, Nagappan; Tylus, Urszula; Strickland, Kara; Li, Jingkun; Serov, Alexey; Artyushkova, Kateryna; Atanassov, Plamen; Anibal, Jacob; Gumeci, Cenk; Barton, Scott Calabrese; Sougrati, Moulay-Tahar; Jaouen, Frederic; Halevi, Barr; Mukerjee, Sanjeev (NEU); (UNM); (CNRS-UMR); (General Motors); (Pajarito); (MSU)

    2016-11-01

    Developing efficient and inexpensive catalysts for the sluggish oxygen reduction reaction (ORR) constitutes one of the grand challenges in the fabrication of commercially viable fuel cell devices and metal–air batteries for future energy applications. Despite recent achievements in designing advanced Pt-based and Pt-free catalysts, current progress primarily involves an empirical approach of trial-and-error combination of precursors and synthesis conditions, which limits further progress. Rational design of catalyst materials requires proper understanding of the mechanistic origin of the ORR and the underlying surface properties under operating conditions that govern catalytic activity. Herein, several different groups of iron-based catalysts synthesized via different methods and/or precursors were systematically studied by combining multiple spectroscopic techniques under ex situ and in situ conditions in an effort to obtain a comprehensive understanding of the synthesis-products correlations, nature of active sites, and the reaction mechanisms. These catalysts include original macrocycles, macrocycle-pyrolyzed catalysts, and Fe-N–C catalysts synthesized from individual Fe, N, and C precursors including polymer-based catalysts, metal organic framework (MOF)-based catalysts, and sacrificial support method (SSM)-based catalysts. The latter group of catalysts is most promising as not only they exhibit exceptional ORR activity and/or durability, but also the final products are controllable. We show that the high activity observed for most pyrolyzed Fe-based catalysts can mainly be attributed to a single active site: non-planar Fe–N4 moiety embedded in distorted carbon matrix characterized by a high potential for the Fe2+/3+ redox transition in acidic electrolyte/environment. The high intrinsic ORR activity, or turnover frequency (TOF), of this site is shown to be accounted for by redox catalysis mechanism that highlights the dominant role

  4. Insights into the dual activation mechanism involving bifunctional cinchona alkaloid thiourea organocatalysts: an NMR and DFT study.

    Science.gov (United States)

    Zhu, Jun-Ling; Zhang, Yong; Liu, Chong; Zheng, An-Min; Wang, Wei

    2012-11-02

    In-depth understanding of the activation mechanism in asymmetric organocatalysis is of great importance for rational development of highly efficient catalytic systems. In this Article, the mechanism for the direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactam (Nu) and chalcone (EI) catalyzed by the bifunctional cinchona alkaloid thiourea organocatalyst (Cat) was studied with a combination of experimental (NMR) and theoretical (DFT) approaches, through which a new dual activation pathway was found. The key feature of this new dual activation mechanism (Pathway C) is that one N-H(A) of the thiourea moiety and the N-H of the protonated amine in Cat simultaneously activate Nu, while the other N-H(B) of the thiourea moiety activates EI. Both the NMR measurement and the DFT calculation identified that the interaction of Cat with Nu is stronger than that with EI in the catalyst-substrate complexes. Kinetic studies via variable-temperature NMR measurements indicated that, with the experimental activation energy E(a) of 10.2 kcal/mol, the reaction is all first-order in Nu, EI, and Cat. The DFT calculation further revealed that the C-C bond formation is both the rate-determining and the stereoselectivity-controlling steps. In agreement with the experimental data, the energy barrier for the rate-determining step along Pathway C was calculated as 8.8 kcal/mol. The validity of Pathway C was further evidenced by the calculated enantioselectivity (100% ee) and diastereoselectivity (60:1 dr), which are in excellent match with the experimental data (98% ee and >30:1 dr, respectively). Mechanistic study on the Michael addition of nitromethane to chalcone catalyzed by the Catalyst I further identified the generality of this new dual activation mechanism in cinchona alkaloid thiourea organocatalysis.

  5. Physical activity in patients with type 2 diabetes and hypertension – insights into motivations and barriers from the MOBILE study

    Directory of Open Access Journals (Sweden)

    Duclos M

    2015-06-01

    Full Text Available Martine Duclos,1,2 Sylvie Dejager,3,4 Nicolas Postel-Vinay,5 Sylvie di Nicola,6 Stéphane Quéré,7 Béatrice Fiquet4,5 1Department of Sport Medicine and Functional Explorations, University-Hospital (CHU, G Montpied Hospital; INRA, UNH, CRNH Auvergne, 2Nutrition Department, University of Auvergne, Clermont-Ferrand, Auvergne, 3Department of Endocrinology and Metabolism, La Pitié-Salpétrière Hospital, Paris, 4Clinical and Scientific Affairs, Novartis Pharma SAS, Rueil-Malmaison, 5Department of Hypertension, Georges Pompidou European Hospital, Paris, 6Biostatistics, Inferential, Paris, 7Biostatistics, Novartis Pharma SAS, Rueil-Malmaison, France Background: Although physical activity (PA is key in the management of type 2 diabetes (T2DM and hypertension, it is difficult to implement in practice. Methods: Cross-sectional, observational study. Participating physicians were asked to recruit two active and four inactive patients, screened with the Ricci-Gagnon (RG self-questionnaire (active if score ≥16. Patients subsequently completed the International Physical Activity Questionnaire. The objective was to assess the achievement of individualized glycated hemoglobin and blood pressure goals (<140/90 mmHg in the active vs inactive cohort, to explore the correlates for meeting both targets by multivariate analysis, and to examine the barriers and motivations to engage in PA. Results: About 1,766 patients were analyzed. Active (n=628 vs inactive (n=1,138 patients were more often male, younger, less obese, had shorter durations of diabetes, fewer complications and other health issues, such as osteoarticular disorders (P<0.001 for all. Their diabetes and hypertension control was better and obtained despite a lower treatment burden. The biggest difference in PA between the active vs inactive patients was the percentage who declared engaging in regular leisure-type PA (97.9% vs 9.6%, also reflected in the percentage with vigorous activities in

  6. Active and passive smoking - New insights on the molecular composition of different cigarette smoke aerosols by LDI-FTICRMS

    Science.gov (United States)

    Schramm, Sébastien; Carré, Vincent; Scheffler, Jean-Luc; Aubriet, Frédéric

    2014-08-01

    The aerosol generated when a cigarette is smoked is a significant indoor contaminant. Both smokers and non-smokers can be exposed to this class of pollutants. Nevertheless, they are not exposed to the same kind of smoke. The active smoker breathes in the mainstream smoke (MSS) during a puff, whereas the passive smoker inhales not only the smoke generated by the lit cigarette between two puffs (SSS) but also the smoke exhaled by active smokers (EXS). The aerosol fraction of EXS has until now been poorly documented; its composition is expected to be different from MSS. This study aims to investigate the complex composition of aerosol from EXS to better understand the difference in exposure between active and passive smokers. To address this, the in-situ laser desorption ionisation Fourier transform ion cyclotron mass spectrometry (LDI-FTICRMS) was used to characterise the aerosol composition of EXS from two different smokers. Results clearly indicated many similarities between EXS samples but also significant differences with MSS and SSS aerosol. The comparison of MSS and EXS aerosol allowed the chemicals retained by the active smoker's lungs to be identified, whereas the convolution of the EXS and SSS aerosol compositions were considered relevant to the exposition of a passive smoker. As a consequence, active smokers are thought to be mainly exposed to polar and poorly unsaturated oxygenated and nitrogenated organics, compared with poorly oxygenated but highly unsaturated compounds in passive smokers.

  7. Insights into seasonal variation of litter decomposition and related soil degradative enzyme activities in subtropical forest in China

    Institute of Scientific and Technical Information of China (English)

    WANG Cong-yan; LÜ Yan-na; WANG Lei; LIU Xue-yan; TIAN Xing-jun

    2013-01-01

    We used a litterbag method to investigate litter decomposition and related soil degradative enzyme activities across four seasons in a broad-leaved forest and a coniferous forest on Zijin Mountain in sub-tropical China. Across four seasons, we quantified litter mass losses, soil pH values, and related soil degradative enzyme activities. Litter decomposition rates differed significantly by season. Litter decomposi-tion rates of broadleaf forest leaves were higher than for coniferous for-ests needles across four seasons, and maximal differences in litter de-composition rates between the two litter types were found in spring. Obvious differences in litter decomposition rates of the two litter types were found in winter, which were similar to rates in spring. Litter de-composition rates of the two litter types in autumn were significantly higher than in spring. Soil degradative enzyme activities were lowest in winter and highest in summer in most cases across four seasons.

  8. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state.

    Directory of Open Access Journals (Sweden)

    Elham Schokraie

    Full Text Available Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.

  9. Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state.

    Science.gov (United States)

    Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A; Hengherr, Steffen; Förster, Frank; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

    2012-01-01

    Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.

  10. Digestive enzyme activities in the guts of bonnethead sharks (Sphyrna tiburo) provide insight into their digestive strategy and evidence for microbial digestion in their hindguts.

    Science.gov (United States)

    Jhaveri, Parth; Papastamatiou, Yannis P; German, Donovan P

    2015-11-01

    Few investigations have studied digestive enzyme activities in the alimentary tracts of sharks to gain insight into how these organisms digest their meals. In this study, we examined the activity levels of proteases, carbohydrases, and lipase in the pancreas, and along the anterior intestine, spiral intestine, and colon of the bonnethead shark, Sphyrna tiburo. We then interpreted our data in the context of a rate-yield continuum to discern this shark's digestive strategy. Our data show anticipated decreasing patterns in the activities of pancreatic enzymes moving posteriorly along the gut, but also show mid spiral intestine peaks in aminopeptidase and lipase activities, which support the spiral intestine as the main site of absorption in bonnetheads. Interestingly, we observed spikes in the activity levels of N-acetyl-β-D-glucosaminidase and β-glucosidase in the bonnethead colon, and these chitin- and cellulose-degrading enzymes, respectively, are likely of microbial origin in this distal gut region. Taken in the context of intake and relatively long transit times of food through the gut, the colonic spikes in N-acetyl-β-D-glucosaminidase and β-glucosidase activities suggest that bonnetheads take a yield-maximizing strategy to the digestive process, with some reliance on microbial digestion in their hindguts. This is one of the first studies to examine digestive enzyme activities along the gut of any shark, and importantly, the data match with previous observations that sharks take an extended time to digest their meals (consistent with a yield-maximizing digestive strategy) and that the spiral intestine is the primary site of absorption in sharks.

  11. Empirical Studies on Actively Managed Mutual Funds: New Insights into the Costs and Benefits of Portfolio Disclosure

    NARCIS (Netherlands)

    T.C. Dyakov (Teodor)

    2014-01-01

    markdownabstract__Abstract__ Dyakov’s dissertation bundles three empirical studies on actively managed mutual funds. His studies provide new knowledge of the costs and benefits of portfolio disclosure and shed more light into the question whether mutual fund investors have an information advantage

  12. Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD(50) yields insight into the efficacy of prophylactics.

    Science.gov (United States)

    Marziaz, Mandy L; Frazier, Kathryn; Guidry, Paul B; Ruiz, Robyn A; Petrikovics, Ilona; Haines, Donovan C

    2013-01-01

    Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems.

  13. Insights into the Thiamine Diphosphate Enzyme Activation Mechanism: Computational Model for Transketolase Using a Quantum Mechanical/Molecular Mechanical Method.

    Science.gov (United States)

    Nauton, Lionel; Hélaine, Virgil; Théry, Vincent; Hecquet, Laurence

    2016-04-12

    We propose the first computational model for transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, using a quantum mechanical/molecular mechanical method on the basis of crystallographic TK structures from yeast and Escherichia coli, together with experimental kinetic data reported in the literature with wild-type and mutant TK. This model allowed us to define a new route for ThDP activation in the enzyme environment. We evidenced a strong interaction between ThDP and Glu418B of the TK active site, itself stabilized by Glu162A. The crucial point highlighted here is that deprotonation of ThDP C2 is not performed by ThDP N4' as reported in the literature, but by His481B, involving a HOH688A molecule bridge. Thus, ThDP N4' is converted from an amino form to an iminium form, ensuring the stabilization of the C2 carbanion or carbene. Finally, ThDP activation proceeds via an intermolecular process and not by an intramolecular one as reported in the literature. More generally, this proposed ThDP activation mechanism can be applied to some other ThDP-dependent enzymes and used to define the entire TK mechanism with donor and acceptor substrates more accurately.

  14. Domain organization of DNase from Thioalkalivibrio sp. provides insights into retention of activity in high salt environments

    Directory of Open Access Journals (Sweden)

    Gediminas eAlzbutas

    2015-07-01

    Full Text Available Our study indicates that DNA binding domains are common in many halophilic or halotolerantbacterial DNases and they are potential activators of enzymatic activity at high ionic strength.Usually, proteins adapt to high ionic strength by increasing the number of negatively chargedresidues on the surface. However, in DNases such adaptation would hinder the binding to negativelycharged DNA, a step critical for catalysis. In our study we demonstrate how evolution hassolved this dilemma by engaging the DNA binding domain. We propose a mechanism, whichenables the enzyme activity at salt concentrations as high as 4 M of sodium chloride, based oncollected experimental data and domain structure analysis of a secreted bacterial DNase fromthe extremely halotolerant bacterium Thioalkalivibrio sp. K90mix. The enzyme harbors twodomains: an N-terminal domain, that exhibits DNase activity, and a C-terminal domain, comprisinga duplicate DNA binding helix-hairpin-helix motif. Here we present experimental datademonstrating that the C-terminal domain is responsible for the enzyme’s resistance to highionic strength.

  15. Activities of Secreted Aryl Alcohol Quinone Oxidoreductases from Pycnoporus cinnabarinus Provide Insights into Fungal Degradation of Plant Biomass.

    Science.gov (United States)

    Mathieu, Yann; Piumi, Francois; Valli, Richard; Aramburu, Juan Carro; Ferreira, Patricia; Faulds, Craig B; Record, Eric

    2016-04-01

    Auxiliary activities family 3 subfamily 2 (AA3_2) from the CAZy database comprises various functions related to ligninolytic enzymes, such as fungal aryl alcohol oxidases (AAO) and glucose oxidases, both of which are flavoenzymes. The recent study of the Pycnoporus cinnabarinus CIRM BRFM 137 genome combined with its secretome revealed that four AA3_2 enzymes are secreted during biomass degradation. One of these AA3_2 enzymes, scf184803.g17, has recently been produced heterologously in Aspergillus niger Based on the enzyme's activity and specificity, it was assigned to the glucose dehydrogenases (PcinnabarinusGDH [PcGDH]). Here, we analyze the distribution of the other three AA3_2 enzymes (scf185002.g8, scf184611.g7, and scf184746.g13) to assess their putative functions. These proteins showed the highest homology with aryl alcohol oxidase from Pleurotus eryngii Biochemical characterization demonstrated that they were also flavoenzymes harboring flavin adenine dinucleotide (FAD) as a cofactor and able to oxidize a wide variety of phenolic and nonphenolic aryl alcohols and one aliphatic polyunsaturated primary alcohol. Though presenting homology with fungal AAOs, these enzymes exhibited greater efficiency in reducing electron acceptors (quinones and one artificial acceptor) than molecular oxygen and so were defined as aryl-alcohol:quinone oxidoreductases (AAQOs) with two enzymes possessing residual oxidase activity (PcAAQO2 and PcAAQO3). Structural comparison of PcAAQO homology models with P. eryngii AAO demonstrated a wider substrate access channel connecting the active-site cavity to the solvent, explaining the absence of activity with molecular oxygen. Finally, the ability of PcAAQOs to reduce radical intermediates generated by laccase from P. cinnabarinus was demonstrated, shedding light on the ligninolytic system of this fungus.

  16. Differential brain activity states during the perception and nonperception of illusory motion as revealed by magnetoencephalography.

    Science.gov (United States)

    Crowe, David A; Leuthold, Arthur C; Georgopoulos, Apostolos P

    2010-12-28

    We studied visual perception using an annular random-dot motion stimulus called the racetrack. We recorded neural activity using magnetoencephalography while subjects viewed variants of this stimulus that contained no inherent motion or various degrees of embedded motion. Subjects reported seeing rotary motion during viewing of all stimuli. We found that, in the absence of any motion signals, patterns of brain activity differed between states of motion perception and nonperception. Furthermore, when subjects perceived motion, activity states within the brain did not differ across stimuli of different amounts of embedded motion. In contrast, we found that during periods of nonperception brain-activity states varied with the amount of motion signal embedded in the stimulus. Taken together, these results suggest that during perception the brain may lock into a stable state in which lower-level signals are suppressed.

  17. The study of disk resonators diode modules, solid-state generators active

    Directory of Open Access Journals (Sweden)

    B. A. Kotserzhinskii

    1987-12-01

    Full Text Available The results of an experimental study of disk resonators diode modules, solid-state active microwave generators. The effect of current leads, as well as errors in the manufacture of resonators their characteristics.

  18. Spontaneous brain activity in the default mode network is sensitive to different resting-state conditions with limited cognitive load.

    Directory of Open Access Journals (Sweden)

    Chaogan Yan

    Full Text Available BACKGROUND: Recent functional MRI (fMRI studies have demonstrated that there is an intrinsically organized default mode network (DMN in the resting brain, primarily made up of the posterior cingulate cortex (PCC and the medial prefrontal cortex (MPFC. Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed. METHODOLOGY/PRINCIPAL FINDINGS: Four resting-state fMRI sessions were acquired: 1 eyes-closed (EC (used to generate the DMN mask; 2 EC; 3 eyes-open with no fixation (EO; and 4 eyes-open with a fixation (EO-F. The 2-4 sessions were counterbalanced across participants (n = 20, 10 males. We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF within the DMN among the 2-4 resting-state conditions (i.e., EC, EO, and EO-F. Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity. CONCLUSIONS/SIGNIFICANCE: Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should

  19. Mechanistic Insight into the Rh(III)-Catalyzed C-H Activation of 2-Acetyl-1-Arythydrazines in Water.

    Science.gov (United States)

    Wu, Weirong; Liu, Tao; Huang, Caiyun; Zhang, Jing; Man, Xiaoping

    2017-03-02

    A mechanistic study of the Cp*Rh(III)-catalyzed C-H functionalization of 2-acetyl-1-arythydrazines with diazo compounds in water was carried out by using density functional theory calculations. The results reveal that the acetyl-bonded N-H deprotonation is prior to the phenyl C-H activation. The mechanisms from protonation by acetic acid disagree with the proposal by the Wang group. Different from the Rh(III)-catalyzed C-H activation reported by experimental literature, the rate-determining step of the whole catalytic cycle with an overall barrier of 31.7 kcal mol(-1) (IV → TS12-P') is the protonation process of hydroxy O rather than the C-H bond cleavage step. The present theoretical study rationalizes the experimental observation at the molecular level.

  20. Petrologic insights into basaltic volcanism at historically active Hawaiian volcanoes: Chapter 6 in Characteristics of Hawaiian volcanoes

    Science.gov (United States)

    Helz, Rosalind L.; Clague, David A.; Sisson, Thomas W.; Thornber, Carl R.; Poland, Michael P.; Takahashi, T. Jane; Landowski, Claire M.

    2014-01-01

    Study of the petrology of Hawaiian volcanoes, in particular the historically active volcanoes on the Island of Hawai‘i, has long been of worldwide scientific interest. When Dr. Thomas A. Jaggar, Jr., established the Hawaiian Volcano Observatory (HVO) in 1912, detailed observations on basaltic activity at Kīlauea and Mauna Loa volcanoes increased dramatically. The period from 1912 to 1958 saw a gradual increase in the collection and analysis of samples from the historical eruptions of Kīlauea and Mauna Loa and development of the concepts needed to evaluate them. In a classic 1955 paper, Howard Powers introduced the concepts of magnesia variation diagrams, to display basaltic compositions, and olivine-control lines, to distinguish between possibly comagmatic and clearly distinct basaltic lineages. In particular, he and others recognized that Kīlauea and Mauna Loa basalts must have different sources.

  1. Temporal Patterns of Pedophile Activity in a P2P Network: First Insights about User Profiles from Big Data

    OpenAIRE

    Fournier, Raphaël; Latapy, Matthieu

    2015-01-01

    International audience; Recent studies have shown that child abuse material is shared through peer-to-peer (P2P) networks, which allow users to exchange files without a central server. Obtaining knowledge on the extent of this activity has major consequences for child protection, policy making and Internet regulation. Previous works have developed tools and analyses to provide overall figures in temporally-limited measurements. Offenders' behavior is mostly studied through small-scale intervi...

  2. Temperature dependence of dc electrical conductivity of activated carbon-metal oxide nanocomposites. Some insight into conduction mechanisms

    Science.gov (United States)

    Barroso-Bogeat, Adrián; Alexandre-Franco, María; Fernández-González, Carmen; Sánchez-González, José; Gómez-Serrano, Vicente

    2015-12-01

    From a commercial activated carbon (AC) and six metal oxide (Al2O3, Fe2O3, SnO2, TiO2, WO3 and ZnO) precursors, two series of AC-metal oxide nanocomposites are prepared by wet impregnation, oven-drying at 120 °C, and subsequent heat treatment at 200 or 850 °C in inert atmosphere. The temperature-dependent dc electrical conductivity of AC and the as-prepared nanocomposites is measured from room temperature up to ca. 200 °C in air atmosphere by the four-probe method. The decrease in conductivity for the hybrid materials as compared to AC is the result of a complex interplay between several factors, including not only the intrinsic conductivity, crystallite size, content and chemical nature of the supported nanoparticles, which ultimately depend on the precursor and heat treatment temperature, but also the adsorption of oxygen and water from the surrounding atmosphere. The conductivity data are discussed in terms of a thermally activated process. In this regard, both AC and the prepared nanocomposites behave as semiconductors, and the temperature-dependent conductivity data have been interpreted on the basis of the classical model proposed by Mott and Davis. Because of its high content of heteroatoms, AC may be considered as a heavily doped semiconductor, so that conduction of thermally excited carriers via acceptor or donor levels is expected to be the dominant mechanism. The activation energies for the hybrid materials suggest that the supported metal oxide nanoparticles strongly modify the electronic band structure of AC by introducing new trap levels in different positions along its band gap. Furthermore, the thermally activated conduction process satisfies the Meyer-Neldel rule, which is likely connected with the shift of the Fermi level due to the introduction of the different metal oxide nanoparticles in the AC matrix.

  3. Hydrothermal fluids circulation and travertine deposition in an active tectonic setting: Insights from the Kamara geothermal area (western Anatolia, Turkey)

    Science.gov (United States)

    Brogi, Andrea; Alçiçek, M. Cihat; Yalçıner, Cahit Çağlar; Capezzuoli, Enrico; Liotta, Domenico; Meccheri, Marco; Rimondi, Valentina; Ruggieri, Giovanni; Gandin, Anna; Boschi, Chiara; Büyüksaraç, Aydin; Alçiçek, Hülya; Bülbül, Ali; Baykara, Mehmet Oruç; Shen, Chuan-Chou

    2016-06-01

    Coexistence of thermal springs, travertine deposits and tectonic activity is a recurring feature for most geothermal areas. Although such a certainty, their relationships are debated mainly addressing on the role of the tectonic activity in triggering and controlling fluids flow and travertine deposition. In this paper, we present the results of an integrated study carried out in a geothermal area located in western Anatolia (Turkey), nearby the well-known Pamukkale area (Denizli Basin). Our study focused on the relationships among hydrothermal fluids circulation, travertine deposition and tectonic activity, with particular emphasis on the role of faults in controlling fluids upwelling, thermal springs location and deposition of travertine masses. New field mapping and structural/kinematics analyses allowed us to recognize two main faults systems (NW- and NE-trending), framed in the Neogene-Quaternary extensional tectonic evolution of western Anatolia. A geo-radar (GPR) prospection was also provided in a key-area, permitting us to reconstruct a buried fault zone and its relationships with the development of a fissure-ridge travertine deposit (Kamara fissure-ridge). The integration among structural and geophysical studies, fluids inclusion, geochemical, isotopic data and 230 Th/238 U radiometric age determination on travertine deposits, depict the characteristics of the geothermal fluids and their pathway, up to the surface. Hydrological and seismological data have been also taken in account to investigate the relation between local seismicity and fluid upwelling. As a main conclusion we found strict relationships among tectonic activity, earthquakes occurrence, and variation of the physical/chemical features of the hydrothermal fluids, presently exploited at depth, or flowing out in thermal springs. In the same way, we underline the tectonic role in controlling the travertine deposition, making travertine (mainly banded travertine) a useful proxy to reconstruct the

  4. Computational Insights into the Inhibitory Mechanism of Human AKT1 by an Orally Active Inhibitor, MK-2206

    OpenAIRE

    Mohd Rehan; Beg, Mohd A.; Shadma Parveen; Ghazi A Damanhouri; Galila F Zaher

    2014-01-01

    The AKT signaling pathway has been identified as an important target for cancer therapy. Among small-molecule inhibitors of AKT that have shown tremendous potential in inhibiting cancer, MK-2206 is a highly potent, selective and orally active allosteric inhibitor. Promising preclinical anticancer results have led to entry of MK-2206 into Phase I/II clinical trials. Despite such importance, the exact binding mechanism and the molecular interactions of MK-2206 with human AKT are not available. ...

  5. State-related differences in the level of psychomotor activity in patients with bipolar disorder

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Maria; Brage, Søren; Vinberg, Maj;

    2016-01-01

    Measuring changes in psychomotor activity is a potential tool in the monitoring of the course of affective states in bipolar disorder. Previous studies have been cross-sectional and only some have used objective measures. The aim was to investigate state-related differences in objectively...

  6. Trends in No Leisure-Time Physical Activity--United States, 1988-2010

    Science.gov (United States)

    Moore, Latetia V.; Harris, Carmen D.; Carlson, Susan A.; Kruger, Judy; Fulton, Janet E.

    2012-01-01

    Purpose: The aim of this study was to examine trends in the prevalence of no leisure-time physical activity (LTPA) from 1988 to 2010. Method: Using the Behavioral Risk Factor Surveillance System data, 35 states and the District of Columbia reported information on no LTPA from 1988 to 1994; all states reported no LTPA from 1996 to 2010. Results: No…

  7. 77 FR 69650 - Agency Information Collection Activities: Holders or Containers Which Enter the United States...

    Science.gov (United States)

    2012-11-20

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Holders or Containers... concerning the Holders or Containers which Enter the United States Duty Free. This request for comment is...: Title: Holders or Containers which Enter the United States Duty Free. OMB Number: 1651-0035. Form...

  8. Structural Insights into the Protease-like Antigen Plasmodium falciparum SERA5 and Its Noncanonical Active-Site Serine

    Energy Technology Data Exchange (ETDEWEB)

    Hodder, Anthony N.; Malby, Robyn L.; Clarke, Oliver B.; Fairlie, W. Douglas; Colman, Peter M.; Crabb, Brendan S.; Smith, Brian J.; (WEHIMR); (Melbourne)

    2009-08-28

    The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putative nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S{sub 2} specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.

  9. Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

    Science.gov (United States)

    Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

    2009-06-01

    Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

  10. The INSIGHT SEIS VBB Experiment

    Science.gov (United States)

    Tillier, S.; De Raucourt, S.; Lognonne, P. H.; Banerdt, B.; Mimoun, D.; Giardini, D.; Christensen, U. R.; Pike, W. T.; Zweifel, P.; Mance, D.; Bierwirth, M.; Laudet, P.; Perez, R.; Kerjean, L.; Hurst, K. J.; Mocquet, A.; Garcia, R. F.

    2012-12-01

    The SEIS experiment is the primary payload of the Interior Structure investigation using Seismology and Heat Transport (INSIGHT) Mission Proposal, submitted to NASA in the frame of the 2010 Discovery program, and selected for a competitive phase A study, together with two other projects. The objective of the INSIGHT SEIS experiment is the determination of the deep internal structure of Mars. In particular, geophysical parameters of first importance, such as the state (liquid/solid) and size of the core, structure of the mantle, shape of discontinuities, thickness of the crust will be determined by the experiment. It will measure seismic activity in a very broad band of signal, from the tidal frequencies (0.05 mHz) up to the short period frequencies (50 Hz), to address the widest range of scientific questions, from the state of the core to the meteoritic impact and quake rates. The instrument integrates a Very Broad Band (VBB) 3 axis seismometer, completed by another trihedron of MEMS short period seismometers, environmental sensors for pressure, wind and temperature, The sensors will be deployed on the Martian ground by a robotic arm from a Phoenix-type lander platform and protected by a wind and thermal shield. The sensor assembly, which contains all seismic sensors, the leveling system, as well as house-keeping and temperature measurements, will be deployed on the soil in order to allow the best possible mechanical coupling with the ground motion. The wind and thermal shield, the sensors' specific containers (vacuum sphere for VBBs) and a passive thermal compensation system will achieve a very high protection of the VBB against temperature and pressure variations, allowing the sensor to operate in the rough Martian thermal environment while reaching a deection threshold below 10-9 ms-2 Hz-1/2 in the VBB bandwidth. A dedicated electronics will manage the overall experiment and ultra-low noise, space qualified 24 bits A/D converters will perform the acquisition

  11. Volcanic and Tectonic Activity in the Red Sea Region (2004-2013): Insights from Satellite Radar Interferometry and Optical Imagery

    KAUST Repository

    Xu, Wenbin

    2015-04-01

    Studying recent volcanic and tectonic events in the Red Sea region is important for improving our knowledge of the Red Sea plate boundary and for regional geohazard assessments. However, limited information has been available about the past activity due to insufficient in-situ data and remoteness of some of the activity. In this dissertation, I have used satellite remote sensing to derive new information about several recent volcanic and tectonic events in the Red Sea region. I first report on three volcanic eruptions in the southern Red Sea, the 2007-8 Jebel at Tair eruption and the 2011-12 & 2013 Zubair eruptions, which resulted in formation of two new islands. Series of high- resolution optical images were used to map the extent of lava flows and to observe and analyze the growth and destructive processes of the new islands. I used Interferometric Synthetic Aperture Radar (InSAR) data to study the evolution of lava flows, to estimate their volumes, as well as to generate ground displacements maps, which were used to model the dikes that fed the eruptions. I then report on my work of the 2009 Harrat Lunayyir dike intrusion and the 2004 Tabuk earthquake sequence in western Saudi Arabia. I used InSAR observations and stress calculations to study the intruding dike at Harrat Lunayyir, while I combined InSAR data and Bayesian estimation to study the Tabuk earthquake activity. The key findings of the thesis are: 1) The recent volcanic eruptions in the southern Red Sea indicate that the area is magmatically more active than previously acknowledged and that a rifting episode has been taken place in the southern Red Sea; 2) Stress interactions between an ascending dike intrusion and normal faulting on graben-bounding faults above the dike can inhibit vertical propagation of magma towards the surface; 3) InSAR observations can improve locations of shallow earthquakes and fault model uncertainties are useful to associate earthquake activity with mapped faults; 4). The

  12. Encoding of social state information by neuronal activities in the macaque caudate nucleus.

    Science.gov (United States)

    Santos, Gustavo S; Nagasaka, Yasuo; Fujii, Naotaka; Nakahara, Hiroyuki

    2012-01-01

    Social animals adjust their behavior according to social relationships and momentary circumstances. Dominant-submissive relationships modulate, but do not completely determine, their competitive behaviors. For example, a submissive monkey's decision to retrieve food depends not only on the presence of dominant partners but also on their observed behavior. Thus, behavioral expression requires a dynamic evaluation of reward outcome and momentary social states. The neural mechanisms underlying this evaluation remain elusive. The caudate nucleus (CN) plays a pivotal role in representing reward expectation and translating it into action selection. To investigate whether their activities encode social state information, we recorded from CN neurons in monkeys while they performed a competitive food-grab task against a dominant competitor. We found two groups of CN neurons: one primarily responded to reward outcome, while the other primarily tracked the monkey's social state. These social state-dependent neurons showed greater activity when the monkeys freely retrieved food without active challenges from the competitor and reduced activity when the monkeys were in a submissive state due to the competitor's active behavior. These results indicate that different neuronal activities in the CN encode social state information and reward-related information, which may contribute to adjusting competitive behavior in dynamic social contexts.

  13. Mycoplasma suis infection results endothelial cell damage and activation: new insight into the cell tropism and pathogenicity of hemotrophic mycoplasma

    Directory of Open Access Journals (Sweden)

    Sokoli Albina

    2013-02-01

    Full Text Available Abstract Hemotrophic mycoplasmas (HM are highly specialized red blood cell parasites that cause infectious anemia in a variety of mammals, including humans. To date, no in vitro cultivation systems for HM have been available, resulting in relatively little information about the pathogenesis of HM infection. In pigs, Mycoplasma suis-induced infectious anemia is associated with hemorrhagic diathesis, and coagulation dysfunction. However, intravasal coagulation and subsequent consumption coagulopathy can only partly explain the sequence of events leading to hemorrhagic diathesis manifesting as cyanosis, petechial bleeding, and ecchymosis, and to disseminated coagulation. The involvement of endothelial activation and damage in M. suis-associated pathogenesis was investigated using light and electron microscopy, immunohistochemistry, and cell sorting. M. suis interacted directly with endothelial cells in vitro and in vivo. Endothelial activation, widespread endothelial damage, and adherence of red blood cells to the endothelium were evident in M. suis-infected pigs. These alterations of the endothelium were accompanied by hemorrhage, intravascular coagulation, vascular occlusion, and massive morphological changes within the parenchyma. M. suis biofilm-like microcolonies formed on the surface of endothelial cells, and may represent a putative persistence mechanism of M. suis. In vitro analysis demonstrated that M. suis interacted with the endothelial cytoskeletal protein actin, and induced actin condensation and activation of endothelial cells, as determined by the up-regulation of ICAM, PECAM, E-selectin, and P-selectin. These findings demonstrate an additional cell tropism of HM for endothelial cells and suggest that M. suis interferes with the protective function of the endothelium, resulting in hemorrhagic diathesis.

  14. A STATE AS AN ACTIVATOR OF SCIENTIFIC, TECHNICAL AND INNOVATION ACTIVITIES

    Directory of Open Access Journals (Sweden)

    O. Zhylinska

    2013-03-01

    Full Text Available Modern mechanisms and instruments of state regulation of science, technology and innovation are systematized from the point of view of market failures overcoming in these areas of the economy.

  15. Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons.

    Science.gov (United States)

    Ma, Ying; Shaik, Mohammed A; Kozberg, Mariel G; Kim, Sharon H; Portes, Jacob P; Timerman, Dmitriy; Hillman, Elizabeth M C

    2016-12-27

    Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI.

  16. Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms.

    Science.gov (United States)

    Ramsay, Andrew J; Quesada, Victor; Sanchez, Mayka; Garabaya, Cecilia; Sardà, María P; Baiget, Montserrat; Remacha, Angel; Velasco, Gloria; López-Otín, Carlos

    2009-10-01

    Mutations leading to abrogation of matriptase-2 proteolytic activity in humans are associated with an iron-refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. Here we describe two novel heterozygous mutations within the matriptase-2 (TMPRSS6) gene of monozygotic twin girls exhibiting an IRIDA phenotype. The first is the frameshift mutation (P686fs) caused by the insertion of the four nucleotides CCCC in exon 16 (2172_2173insCCCC) that is predicted to terminate translation before the catalytic serine. The second mutation is the di-nucleotide substitution c.467C>A and c.468C>T in exon 3 that causes the missense mutation A118D in the SEA domain of the extracellular stem region of matriptase-2. Functional analysis of both variant matriptase-2 proteases has revealed that they lead to ineffective suppression of hepcidin transcription. We also demonstrate that the A118D SEA domain mutation causes an intra-molecular structural imbalance that impairs matriptase-2 activation. Collectively, these results extend the pattern of TMPRSS6 mutations associated with IRIDA and functionally demonstrate that mutations affecting protease regions other than the catalytic domain may have a profound impact in the regulatory role of matriptase-2 during iron deficiency.

  17. A forced damped oscillation framework for undulatory swimming provides new insights into how propulsion arises in active and passive swimming.

    Directory of Open Access Journals (Sweden)

    Amneet Pal Singh Bhalla

    Full Text Available A fundamental issue in locomotion is to understand how muscle forcing produces apparently complex deformation kinematics leading to movement of animals like undulatory swimmers. The question of whether complicated muscle forcing is required to create the observed deformation kinematics is central to the understanding of how animals control movement. In this work, a forced damped oscillation framework is applied to a chain-link model for undulatory swimming to understand how forcing leads to deformation and movement. A unified understanding of swimming, caused by muscle contractions ("active" swimming or by forces imparted by the surrounding fluid ("passive" swimming, is obtained. We show that the forcing triggers the first few deformation modes of the body, which in turn cause the translational motion. We show that relatively simple forcing patterns can trigger seemingly complex deformation kinematics that lead to movement. For given muscle activation, the forcing frequency relative to the natural frequency of the damped oscillator is important for the emergent deformation characteristics of the body. The proposed approach also leads to a qualitative understanding of optimal deformation kinematics for fast swimming. These results, based on a chain-link model of swimming, are confirmed by fully resolved computational fluid dynamics (CFD simulations. Prior results from the literature on the optimal value of stiffness for maximum speed are explained.

  18. Non-innocent additives in a palladium(II)-catalyzed C-H bond activation reaction: insights into multimetallic active catalysts.

    Science.gov (United States)

    Anand, Megha; Sunoj, Raghavan B; Schaefer, Henry F

    2014-04-16

    The role of a widely employed additive (AgOAc) in a palladium acetate-catalyzed ortho-C-H bond activation reaction has been examined using the M06 density functional theory. A new hetero-bimetallic Pd-(μ-OAc)3-Ag is identified as the most likely active species. This finding could have far-reaching implications with respect to the notion of the active species in palladium catalysis in the presence of other metal salt additives.

  19. Decreased electrophysiological activity represents the conscious state of emptiness in meditation.

    Science.gov (United States)

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful "thoughtless emptiness (TE)," a "focused attention," and an "open monitoring" task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p waves than a wakeful closed eyes resting condition. A group of participants with none or little meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness.

  20. Decreased Electrophysiological Activity Represents the Conscious State of Emptiness in Meditation

    Directory of Open Access Journals (Sweden)

    Thilo eHinterberger

    2014-02-01

    Full Text Available Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful ‘thoughtless emptiness (TE’, a ‘focused attention’, and an ‘open monitoring’ task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 hours of meditation experience.Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (pOur findings indicate that a conscious state of thoughtless emptiness reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness.

  1. Insights from the docking analysis of biologically active compounds from plant Litsea Genus as potential COX-2 inhibitors.

    Science.gov (United States)

    Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan; Bordoloi, Manabjyoti; Sarmah, Rajeev; Bora, Tarun Chandra

    2012-01-01

    Litsea spp of Laural family are traditionally used as herbal medicine for treating inflammation including gastroenterologia, oedema and rheumatic arthritis. Therefore, it is of interest to investigate and understand the molecular principles for such actions. Here, we have illustrated the binding of thirteen Litsea derived biologically active compounds against the inflammation associated target COX (cyclo-oxygenase) -2 enzymes. We compared the binding information of these compounds with a selected number of already known COX-2 inhibitors. The comparison reflected that some of these compounds such as linderol, catechin, 6'-hydroxy-2',3',4' - trimethoxy-chalcone and litseaone have better or equivalent binding features compared to already known inhibitory compounds namely celecoxib, acetylsalicylic acid, rofecoxib. Therefore, all these small compounds reported from plant Litsea spp were found to possess potential medicinal values with anti-inflammatory properties.

  2. New insight on the interaction of self-activated and Mn-related emission centers in ZnS

    Science.gov (United States)

    Bacherikov, Yu Yu; Vorona, I.; Zhuk, A.; Gilchuk, A. V.; Korsunska, N.; Markevich, I.

    2017-02-01

    The photoluminescence (PL) and PL excitation (PLE) spectra of undoped and thermally doped with Mn ZnS single crystals are studied. In the PL spectra, the bands caused by Mn-related and self-activated (SA) emission centers were observed. A number of narrow peaks whose intensity enhanced with increasing Mn content were found in the PLE spectra of SA emission. The same peaks were present in the PLE spectra of the Mn-related emission band. Some of these peaks were previously observed in the absorption spectra and attributed to Mn2+ ions. The appearance of Mn-related peaks in the PLE spectra of SA emission is explained by excitation transfer from the Mn2+ ions to SA emission centers. The conditions required for this transfer and possible mechanisms of the process are discussed.

  3. A Blended Learning Approach to Teaching Project Management: A Model for Active Participation and Involvement: Insights from Norway

    Directory of Open Access Journals (Sweden)

    Bassam A. Hussein

    2015-04-01

    Full Text Available The paper demonstrates and evaluates the effectiveness of a blended learning approach to create a meaningful learning environment. We use the term blended learning approach in this paper to refer to the use of multiple or hybrid instructional methods that emphasize the role of learners as contributors to the learning process rather than recipients of learning. Contribution to learning is attained by using in class gaming as pathways that ensure active involvement of learners. Using a blended learning approach is important in order to be able to address different learning styles of the target group. The approach was also important in order to be able to demonstrate different types of challenges, issues and competences needed in project management. Student evaluations of the course confirmed that the use of multiple learning methods and, in particular, in class gaming was beneficial and contributed to a meaningful learning experience.

  4. Insights from the docking analysis of biologically active compounds from plant Litsea Genus as potential COX-2 inhibitors

    Science.gov (United States)

    Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan; Bordoloi, Manabjyoti; Sarmah, Rajeev; Bora, Tarun Chandra

    2012-01-01

    Litsea spp of Laural family are traditionally used as herbal medicine for treating inflammation including gastroenterologia, oedema and rheumatic arthritis. Therefore, it is of interest to investigate and understand the molecular principles for such actions. Here, we have illustrated the binding of thirteen Litsea derived biologically active compounds against the inflammation associated target COX (cyclo-oxygenase) -2 enzymes. We compared the binding information of these compounds with a selected number of already known COX-2 inhibitors. The comparison reflected that some of these compounds such as linderol, catechin, 6'-hydroxy-2',3',4' - trimethoxy-chalcone and litseaone have better or equivalent binding features compared to already known inhibitory compounds namely celecoxib, acetylsalicylic acid, rofecoxib. Therefore, all these small compounds reported from plant Litsea spp were found to possess potential medicinal values with anti-inflammatory properties. PMID:23139590

  5. Quantification of active mitochondrial permeability transition pores using GNX-4975 inhibitor titrations provides insights into molecular identity

    Science.gov (United States)

    Richardson, Andrew P.; Halestrap, Andrew P.

    2016-01-01

    Inhibition of the mitochondrial permeability transition pore (MPTP) by the novel inhibitor GNX-4975 was characterized. Titration of MPTP activity in de-energized rat liver mitochondria allowed determination of the number of GNX-4975-binding sites and their dissociation constant (Ki). Binding sites increased in number when MPTP opening was activated by increasing [Ca2+], phenylarsine oxide (PAO) or KSCN, and decreased when MPTP opening was inhibited with bongkrekic acid (BKA) or ADP. Values ranged between 9 and 50 pmol/mg of mitochondrial protein, but the Ki remained unchanged at ∼1.8 nM when the inhibitor was added before Ca2+. However, when GNX-4975 was added after Ca2+ it was much less potent with a Ki of ∼140 nM. These data imply that a protein conformational change is required to form the MPTP complex and generate the GNX-4975-binding site. Occupation of the latter with GNX-4975 prevents the Ca2+ binding that triggers pore opening. We also demonstrated that GNX-4975 stabilizes an interaction between the adenine nucleotide translocase (ANT), held in its ‘c’ conformation with carboxyatractyloside (CAT), and the phosphate carrier (PiC) bound to immobilized PAO. No components of the F1Fo-ATP synthase bound significantly to immobilized PAO. Our data are consistent with our previous proposal that the MPTP may form at an interface between the PiC and ANT (or other similar mitochondrial carrier proteins) when they adopt novel conformations induced by factors that sensitize the MPTP to [Ca2+]. We propose that GNX-4975 binds to this interface preventing a calcium-triggered event that opens the interface into a pore. PMID:26920024

  6. Preventing premature deaths from breast and cervical cancer among underserved women in the United States: insights gained from a national cancer screening program.

    Science.gov (United States)

    White, Mary C; Wong, Faye L

    2015-05-01

    This commentary highlights some of the valuable insights gained from a special collection of papers that utilized data from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and appear in this special issue. The data and experiences of the NBCCEDP can inform the identification of new opportunities and directions for meeting the cancer screening needs of underserved women in a complex and changing health care environment.

  7. Self-efficacy for physical activity and insight into its benefits are modifiable factors associated with physical activity in people with COPD a mixed-methods study

    NARCIS (Netherlands)

    Hartman, Jorine E.; ten Hacken, Nick H. T.; Boezen, H. Marike; de Greef, Mathieu H. G.

    2013-01-01

    Questions: What are the perceived reasons for people with chronic obstructive pulmonary disease (COPD) to be physically active or sedentary? Are those reasons related to the actual measured level of physical activity? Design: A mixed-methods study combining qualitative and quantitative approaches. P

  8. New insights into the dynamics and morphology of P3HT:PCBM active layers in bulk heterojunctions.

    Science.gov (United States)

    Carrillo, Jan-Michael Y; Kumar, Rajeev; Goswami, Monojoy; Sumpter, Bobby G; Brown, W Michael

    2013-11-07

    Organic photovoltaics (OPVs) are a topic of extensive research because of their potential application in solar cells. Recent work has led to the development of a coarse-grained model for studying poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) blends using molecular simulations. Here we provide further validation of the force field and use it to study the thermal annealing process of P3HT:PCBM blends. A key finding of our study is that, in contrast to a previous report, the annealing process does not converge at the short time scales reported. Rather, we find that the self-assembly of the blends is characterized by three rate dependent stages that require much longer simulations to approach convergence. Using state-of-the-art high performance computing, we are able to study annealing at length and time scales commensurate with devices used in experiments. Our simulations show different phase segregated morphologies dependent on the P3HT chain length and PCBM volume fraction in the blend. For short chain lengths, we observed a smectic morphology containing alternate P3HT and PCBM domains. In contrast, a phase segregated morphology containing domains of P3HT and PCBM distributed randomly in space is found for longer chain lengths. Theoretical arguments justifying stabilization of these morphologies due to shape anisotropy of P3HT (rod-like) and PCBM (sphere-like) are presented. Furthermore, results on the structure factor, miscibility of P3HT and PCBM, domain spacing and kinetics of phase segregation in the blends are presented in detail. Qualitative comparison of these results with published small-angle neutron scattering experiments in the literature is presented and an excellent agreement is found.

  9. Structure-activity relationships for the fluorescence of ochratoxin A: Insight for detection of ochratoxin A metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Frenette, Christine; Paugh, Robert J. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Tozlovanu, Mariana; Juzio, Maud [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France); Pfohl-Leszkowicz, Annie [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France)], E-mail: leszkowicz@ensat.fr; Manderville, Richard A. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)], E-mail: rmanderv@uoguelph.ca

    2008-06-09

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that is widely found as a contaminant of food products. The toxin is a renal carcinogen in male rats, the cause of mycotoxicoses in pigs and has been associated with chronic human kidney diseases. Bioactivation has been implicated in OTA-mediated toxicity, although inconsistent results have been reported, due, in part, to the difficulty in detecting OTA metabolites in vivo. Liquid chromatography (LC) coupled with fluorescence detection (FLD) is the most widely used analytical detection method for OTA. Under acidic conditions the toxin generates blue fluorescence (465 nm) that is due to an excited state intramolecular proton transfer (ESIPT) process that generates an emissive keto tautomer. Disruption of this ESIPT process quenches fluorescence intensity and causes a blue shift in emission maxima. The aim of the present study was to determine the impact of the C5-chlorine atom, the lactone moiety and the amide bond on OTA fluorescence and derive optical parameters for OTA metabolites that have been detected in vitro. Our results highlight the limitations of LC/FLD for OTA metabolites that do not undergo ESIPT. For emissive derivatives, our absorption and emission data improves the sensitivity of LC/FLD (3-4-fold increase in the limit of detection (LOD)) for OTA analogues bearing a C5-OH group, such as the hydroquinone (OTHQ) metabolite and the glutathione conjugate of OTA (OTA-GSH). This increased sensitivity may facilitate the detection of OTA metabolites bearing a C5-OH group in biological fluids and enhance our understanding of OTA-mediated toxicity.

  10. Hierarchical Model-Based Activity Recognition With Automatic Low-Level State Discovery

    Directory of Open Access Journals (Sweden)

    Justin Muncaster

    2007-09-01

    Full Text Available Activity recognition in video streams is increasingly important for both the computer vision and artificial intelligence communities. Activity recognition has many applications in security and video surveillance. Ultimately in such applications one wishes to recognize complex activities, which can be viewed as combination of simple activities. In this paper, we present a general framework of a Dlevel dynamic Bayesian network to perform complex activity recognition. The levels of the network are constrained to enforce state hierarchy while the Dth level models the duration of simplest event. Moreover, in this paper we propose to use the deterministic annealing clustering method to automatically define the simple activities, which corresponds to the low level states of observable levels in a Dynamic Bayesian Networks. We used real data sets for experiments. The experimental results show the effectiveness of our proposed method.

  11. Tropomyosin structure and function new insights.

    Science.gov (United States)

    Muthuchamy, M; Rethinasamy, P; Wieczorek, D F

    1997-05-01

    Cardiac muscle contraction is dependent upon a cooperative interaction between thick and thin filament sarcomeric proteins. Tropomyosin (TM), an essential thin filament protein, interacts with actin and the troponin complex to regulate contractile activity. During muscle contraction, an increase of calcium (Ca(2+)) in the myofilament space promotes binding of Ca(2+) to troponin C, which alters the conformational state of TM and facilitates acto-myosin interactions. By coupling classic genetic approaches with recent developments in transgenic animal model systems, new insights have been provided on the functional role of TM isoforms in both normal and disease states. The focus of this article is to review the current state of knowledge on TM structure and function, with a particular emphasis on myocardial expression in transgenic mouse model systems. (Trends Cardiovasc Med 1997;7:124-128). © 1997, Elsevier Science Inc.

  12. A Novel Insight to the Functional Role of Stathmin 1 in IgE-Mediated Activation of RBL-2H3 Cells

    Directory of Open Access Journals (Sweden)

    Arthur J.G Moir

    2011-06-01

    Full Text Available IgE-mediated cell signaling, induced by cross-linking of high affinity receptor for IgE (FcεRI in the presence of antigen (Ag, is a well known mechanism described for mast cell activation in allergy and hypersensitivity reactions, which induces a spectrum of cellular responses such as secretion and up-regulation of cell surface FcεRI. Although for several years  IgE  binding  to  FcεRI  was  considered  to  be  a  passive  sensitization  process,  the outcomes of several recent studies have revealed a variety of different cellular responses to IgE binding compared to IgE plus Antigen binding.The present study applied a functional proteomics-based approach to investigate mast cell signaling events and provided new insights to FcεRI-mediated cell signaling in RBL-2H3.1 cells, and may point to the activation of alternative signaling pathways in response to IgE or IgE plus Ag. Comparative analysis by 2-D PAGE of RBL cells activated with IgE plus Ag for  three  and  four  hours  compared  to  non-activated  cells  was  followed  by  mass spectrometric protein identification and provided evidence for the induction of Stathmin 1 (STMN1 gene expression in response to IgE plus Ag activation.Complementary  SDS-PAGE  analysis  showed  a  distinct  up-regulation  of  STMN1 induction in response to challenge with IgE plus Ag compared to sensitization with IgE only. Phosphoproteomics analysis gave evidence for significant increase at phosphorylation of STMN1 on ser16 after 1min, though a slight rise at 5 min, and on ser38 after 1 and 5min sensitization with IgE and a similar result was observed for 1min IgE plus Ag-activation.IgE plus Ag-activation was also found to induce the phosphorylation of ser38 to a greater extent than sensitization with IgE. In contrast, IgE alone was more effective than IgE plus Ag at inducing phosphorylation of ser16. Collectively this study provides further insights into the role of stathmin 1

  13. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

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    Kailong Huang

    2014-06-01

    Full Text Available In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB and antibiotic resistance genes (ARGs in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP sludge.

  14. Resonant activation in polymer translocation: new insights into the escape dynamics of molecules driven by an oscillating field.

    Science.gov (United States)

    Pizzolato, N; Fiasconaro, A; Adorno, D Persano; Spagnolo, B

    2010-08-04

    The translocation of molecules across cellular membranes or through synthetic nanopores is strongly affected by thermal fluctuations. In this work we study how the dynamics of a polymer in a noisy environment changes when the translocation process is driven by an oscillating electric field. An improved version of the Rouse model for a flexible polymer has been adopted to mimic the molecular dynamics, by taking into account the harmonic interactions between adjacent monomers and the excluded-volume effect by introducing a Lennard-Jones potential between all beads. A bending recoil torque has also been included in our model. The polymer dynamics is simulated in a two-dimensional domain by numerically solving the Langevin equations of motion. Thermal fluctuations are taken into account by introducing a Gaussian uncorrelated noise. The mean first translocation time of the polymer centre of inertia shows a minimum as a function of the frequency of the oscillating forcing field. This finding represents the first evidence of the resonant activation behaviour in the dynamics of polymer translocation.

  15. Different efficacy of adenosine and NECA derivatives at the human A3 adenosine receptor: insight into the receptor activation switch.

    Science.gov (United States)

    Dal Ben, Diego; Buccioni, Michela; Lambertucci, Catia; Kachler, Sonja; Falgner, Nico; Marucci, Gabriella; Thomas, Ajiroghene; Cristalli, Gloria; Volpini, Rosaria; Klotz, Karl-Norbert

    2014-01-15

    A3 Adenosine receptors are promising drug targets for a number of diseases and intense efforts are dedicated to develop selective agonists and antagonists of these receptors. A series of adenosine derivatives with 2-(ar)-alkynyl chains, with high affinity and different degrees of selectivity for human A3 adenosine receptors was tested for the ability to inhibit forskolin-stimulated adenylyl cyclase. All these derivatives are partial agonists at A3 adenosine receptors; their efficacy is not significantly modified by the introduction of small alkyl substituents in the N(6)-position. In contrast, the adenosine-5'-N-ethyluronamide (NECA) analogs of 2-(ar)-alkynyladenosine derivatives are full A3 agonists. Molecular modeling analyses were performed considering both the conformational behavior of the ligands and the impact of 2- and 5'-substituents on ligand-target interaction. The results suggest an explanation for the different agonistic behavior of adenosine and NECA derivatives, respectively. A sub-pocket of the binding site was analyzed as a crucial interaction domain for receptor activation.

  16. Detoxification of Deoxynivalenol via Glycosylation Represents Novel Insights on Antagonistic Activities of Trichoderma when Confronted with Fusarium graminearum

    Directory of Open Access Journals (Sweden)

    Ye Tian

    2016-11-01

    Full Text Available Deoxynivalenol (DON is a mycotoxin mainly produced by the Fusarium graminearum complex, which are important phytopathogens that can infect crops and lead to a serious disease called Fusarium head blight (FHB. As the most common B type trichothecene mycotoxin, DON has toxic effects on animals and humans, which poses a risk to food security. Thus, efforts have been devoted to control DON contamination in different ways. Management of DON production by Trichoderma strains as a biological control-based strategy has drawn great attention recently. In our study, eight selected Trichoderma strains were evaluated for their antagonistic activities on F. graminearum by dual culture on potato dextrose agar (PDA medium. As potential antagonists, Trichoderma strains showed prominent inhibitory effects on mycelial growth and mycotoxin production of F. graminearum. In addition, the modified mycotoxin deoxynivalenol-3-glucoside (D3G, which was once regarded as a detoxification product of DON in plant defense, was detected when Trichoderma were confronted with F. graminearum. The occurrence of D3G in F. graminearum and Trichoderma interaction was reported for the first time, and these findings provide evidence that Trichoderma strains possess a self-protection mechanism as plants to detoxify DON into D3G when competing with F. graminearum.

  17. Rh(I)-Catalyzed Arylation of Heterocycles via C-H Bond Activation: Expanded Scope Through Mechanistic Insight

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Jared; Berman, Ashley; Bergman, Robert; Ellman, Jonathan

    2007-07-18

    A practical, functional group tolerant method for the Rh-catalyzed direct arylation of a variety of pharmaceutically important azoles with aryl bromides is described. Many of the successful azole and aryl bromide coupling partners are not compatible with methods for the direct arylation of heterocycles using Pd(0) or Cu(I) catalysts. The readily prepared, low molecular weight ligand, Z-1-tert-butyl-2,3,6,7-tetrahydrophosphepine, which coordinates to Rh in a bidentate P-olefin fashion to provide a highly active yet thermally stable arylation catalyst, is essential to the success of this method. By using the tetrafluoroborate salt of the corresponding phosphonium, the reactions can be assembled outside of a glove box without purification of reagents or solvent. The reactions are also conducted in THF or dioxane, which greatly simplifies product isolation relative to most other methods for direct arylation of azoles employing high-boiling amide solvents. The reactions are performed with heating in a microwave reactor to obtain excellent product yields in two hours.

  18. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    OpenAIRE

    Thilo eHinterberger; Stephanie eSchmidt; Tsutomu eKamei; Harald eWalach

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditat...

  19. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.

    Science.gov (United States)

    Hilf, Ricarda J C; Dutzler, Raimund

    2009-01-01

    The X-ray structure of a pentameric ligand-gated ion channel from Erwinia chrysanthemi (ELIC) has recently provided structural insight into this family of ion channels at high resolution. The structure shows a homo-pentameric protein with a barrel-stave architecture that defines an ion-conduction pore located on the fivefold axis of symmetry. In this structure, the wide aqueous vestibule that is encircled by the extracellular ligand-binding domains of the five subunits narrows to a discontinuous pore that spans the lipid bilayer. The pore is constricted by bulky hydrophobic residues towards the extracellular side, which probably serve as barriers that prevent the diffusion of ions. This interrupted pore architecture in ELIC thus depicts a non-conducting conformation of a pentameric ligand-gated ion channel, the thermodynamically stable state in the absence of bound ligand. As ligand binding promotes pore opening in these ion channels and the specific ligand for ELIC has not yet been identified, we have turned our attention towards a homologous protein from the cyanobacterium Gloebacter violaceus (GLIC). GLIC was shown to form proton-gated channels that are activated by a pH decrease on the extracellular side and that do not desensitize after activation. Both prokaryotic proteins, ELIC and GLIC form ion channels that are selective for cations over anions with poor discrimination among monovalent cations, characteristics that resemble the conduction properties of the cation-selective branch of the family that includes acetylcholine and serotonin receptors. Here we present the X-ray structure of GLIC at 3.1 A resolution. The structure reveals a conformation of the channel that is distinct from ELIC and that probably resembles the open state. In combination, both structures suggest a novel gating mechanism for pentameric ligand-gated ion channels where channel opening proceeds by a change in the tilt of the pore-forming helices.

  20. A gel-free approach in vascular smooth muscle cell proteome: perspectives for a better insight into activation

    Directory of Open Access Journals (Sweden)

    Tedeschi Lorena

    2010-03-01

    Full Text Available Abstract Background The use of chromatography coupled with mass spectrometry (MS analysis is a powerful approach to identify proteins, owing to its capacity to fractionate molecules according to different chemical features. The first protein expression map of vascular smooth muscle cells (VSMC was published in 2001 and since then other papers have been produced. The most detailed two-dimensional polyacrylamide gel electrophoresis (2D-PAGE map was presented by Mayr et al who identified 235 proteins, corresponding to the 154 most abundant unique proteins in mouse aortic VSMC. A chromatographic approach aimed at fractionating the VSMC proteome has never been used before. Results This paper describes a strategy for the study of the VSMC proteome. Our approach was based on pre-fractionation with ion exchange chromatography coupled with matrix assisted laser desorption-time of flight mass spectrometry analysis assisted by a liquid chromatography (LC-MALDI-TOF/TOF. Ion exchange chromatography resulted in a good strategy designed to simplify the complexity of the cellular extract and to identify a large number of proteins. Selectivity based on the ion-exchange chemical features was adequate if evaluated on the basis of protein pI. The LC-MALDI approach proved to be highly reproducible and sensitive since we were able to identify up to 815 proteins with a concentration dynamic range of 7 orders of magnitude. Conclusions In our opinion, the large number of identified proteins and the promising quantitative reproducibility made this approach a powerful method to analyze complex protein mixtures in a high throughput way and to obtain statistical data for the discovery of key factors involved in VSMC activation and to analyze a label-free differential protein expression.

  1. Comparison of starch hydrolysis activity and thermal stability of two Bacillus licheniformis alpha-amylases and insights into engineering alpha-amylase variants active under acidic conditions.

    Science.gov (United States)

    Lee, Seunjae; Oneda, Hiroshi; Minoda, Masashi; Tanaka, Akiyoshi; Inouye, Kuniyo

    2006-06-01

    Bacillus licheniformis alpha-amylase (BLA) is widely used in various procedures of starch degradation in the food industry, and a BLA species with improved activity at higher temperature and under acidic conditions is desirable. Two BLA species, designated as PA and MA, have been isolated from the wild-type B. licheniformis strain and a mutant strain, respectively. In this study, their starch-hydrolysis activity and thermal stability were examined. MA showed higher activity than PA, especially at acidic pH (pH 5.0-5.5), and even after 1 h of treatment at 90 degrees C. MA was active in the range of pH 4.0-8.0, which is much wider than that (pH 4.5-7.5) of PA. It was shown that the proton dissociation constants on the acidic and alkaline sides (pKa1 and pKa2) were shifted to more acidic and basic values, respectively, by the mutation of PA to MA. The activation energy and thermodynamic parameters for their thermal inactivation indicate that MA is more thermally stable and catalytically active than PA, suggesting that MA could be useful for glucose-production process coupled with reactions catalyzed by beta-amylase.

  2. Brain activation, affect, and aerobic exercise: an examination of both state-independent and state-dependent relationships.

    Science.gov (United States)

    Petruzzello, S J; Tate, A K

    1997-09-01

    Resting electroencephalograph (EEG) asymmetry is a biological marker of the propensity to respond affectively to, and a measure of change in affect associated with, acute aerobic exercise. This study examined the EEG-affect-exercise relationship. Twenty participants performed each of three randomly assigned 30-min conditions: (a) a nonexercise control, (b) a cycling exercise at 55% VO2max, and (c) a cycling exercise at 70% VO2max. EEG and affect were assessed pre- and 0, 5, 10, 20, and 30 min postcondition. No significant results were seen in the control or 55% conditions. In the 70% exercise condition, greater relative left frontal activation preexercise predicted increased positive affect and reduced state anxiety postexercise. Participants (n = 7) with extreme relative left frontal activation postexercise reported concomitant decreases in anxiety, whereas participants (n = 7) with extreme relative right frontal activation postexercise reported increases in anxiety. These findings (a) replicate prior work, (b) suggest a dose-response intensity effect, and (c) support the idea that exercise is an emotion-eliciting event. Affective responses seem to be mediated in part by differential resting levels of activation in the anterior brain regions. Ongoing anterior brain activation reflected concurrent postexercise affect.

  3. Innovation Activity in the Republic of Kazakhstan: State Controlling and Ways to Increase Management Efficiency

    Directory of Open Access Journals (Sweden)

    DANA SAYLAUOVNA BEKNIYAZOVA

    2016-04-01

    Full Text Available The main goal of the research is to reveal the dominant role of the state in the innovational development of the country and to define promising areas of the cooperation between the state, universities (research institutes and industry in conducting the research activity. At the present time the innovation activity is a locomotive of progressive phenomena in the economy of the country. Herewith, it is noted that in the Republic of Kazakhstan innovation activity, according to its indicators, falls behind the desired efficient result. This article defines the level of the development of innovation entrepreneurship activity in Kazakhstan. It states the problems related to the innovation development due to the current tendencies of the development of economy in the world. It offers measures for stable and dynamic development of the country that includes the notion of the competitiveness and development of innovational schemes of development that are based on efficient interrelation and optimal combination of interests of the state, universities (research institutes and private sector of Kazakhstan. On the basis of the conducted analysis of variables – factors of innovational development - it was revealed that the efficiency of managing innovation activity by governmental authorities was a “primal cause” that had an impact on such indicators as the level of development of innovational infrastructure and wealth of the country. The authors also proposed the measures of state regulation of the innovation development of enterprises and stimulation of partnership of the science with the production.

  4. Students’ Extracurricular Activities in Higher Education and Its Effect on Personal Development and Academic Achievement (Case Study In Islamic State University of Suska Riau

    Directory of Open Access Journals (Sweden)

    Amirah Diniaty

    2014-11-01

    Full Text Available This study investigates the students’ extracurricular activities at Islamic State University of Suska Riau concerning the types and forms of their activities, background of the activity, benefits of extracurricular activities, and its effect on students’ self-development and academic achievement. 300 students who enroll at sixth semester in eight Faculties (Tarbiyah and Teacher’s Training, Sharia and Law, Ushuludin, Dakwah and Communication Sciences, Science and Technology, Psychology, Economics and Social Sciences, Agriculture and Animal Husbandry were the sample of this study. The data were then processed statistically using percentages and regression of correlation. It was found that the type of extracurricular followed by the students were leadership (70%, those of whom had the motivation to add insight, knowledge and more critical thinking were (44.67%. Some students followed extra-curricular activity because of their solicitation or to follow the main stream (37%, some students did not get financial benefits from the activity (34.67%. Some other respondents felt that they could follow the extracurricular talents, interests and personal abilities (58.67%, and think about their future after graduating from the college (66%. Things need to be followed up by students and university staffs were the more active students who attend the extracurricular activities were the lower achievement ones. Copyright © 2014 by Al-Ta'lim All right reserved

  5. Animal-borne imaging reveals novel insights into the foraging behaviors and Diel activity of a large-bodied apex predator, the American alligator (Alligator mississippiensis.

    Directory of Open Access Journals (Sweden)

    James C Nifong

    Full Text Available Large-bodied, top- and apex predators (e.g., crocodilians, sharks, wolves, killer whales can exert strong top-down effects within ecological communities through their interactions with prey. Due to inherent difficulties while studying the behavior of these often dangerous predatory species, relatively little is known regarding their feeding behaviors and activity patterns, information that is essential to understanding their role in regulating food web dynamics and ecological processes. Here we use animal-borne imaging systems (Crittercam to study the foraging behavior and activity patterns of a cryptic, large-bodied predator, the American alligator (Alligator mississippiensis in two estuaries of coastal Florida, USA. Using retrieved video data we examine the variation in foraging behaviors and activity patterns due to abiotic factors. We found the frequency of prey-attacks (mean = 0.49 prey attacks/hour as well as the probability of prey-capture success (mean = 0.52 per attack were significantly affected by time of day. Alligators attempted to capture prey most frequently during the night. Probability of prey-capture success per attack was highest during morning hours and sequentially lower during day, night, and sunset, respectively. Position in the water column also significantly affected prey-capture success, as individuals' experienced two-fold greater success when attacking prey while submerged. These estimates are the first for wild adult American alligators and one of the few examples for any crocodilian species worldwide. More broadly, these results reveal that our understandings of crocodilian foraging behaviors are biased due to previous studies containing limited observations of cryptic and nocturnal foraging interactions. Our results can be used to inform greater understanding regarding the top-down effects of American alligators in estuarine food webs. Additionally, our results highlight the importance and power of using animal

  6. Animal-Borne Imaging Reveals Novel Insights into the Foraging Behaviors and Diel Activity of a Large-Bodied Apex Predator, the American Alligator (Alligator mississippiensis)

    Science.gov (United States)

    Nifong, James C.; Nifong, Rachel L.; Silliman, Brian R.; Lowers, Russell H.; Guillette, Louis J.; Ferguson, Jake M.; Welsh, Matthew; Abernathy, Kyler; Marshall, Greg

    2014-01-01

    Large-bodied, top- and apex predators (e.g., crocodilians, sharks, wolves, killer whales) can exert strong top-down effects within ecological communities through their interactions with prey. Due to inherent difficulties while studying the behavior of these often dangerous predatory species, relatively little is known regarding their feeding behaviors and activity patterns, information that is essential to understanding their role in regulating food web dynamics and ecological processes. Here we use animal-borne imaging systems (Crittercam) to study the foraging behavior and activity patterns of a cryptic, large-bodied predator, the American alligator (Alligator mississippiensis) in two estuaries of coastal Florida, USA. Using retrieved video data we examine the variation in foraging behaviors and activity patterns due to abiotic factors. We found the frequency of prey-attacks (mean = 0.49 prey attacks/hour) as well as the probability of prey-capture success (mean = 0.52 per attack) were significantly affected by time of day. Alligators attempted to capture prey most frequently during the night. Probability of prey-capture success per attack was highest during morning hours and sequentially lower during day, night, and sunset, respectively. Position in the water column also significantly affected prey-capture success, as individuals’ experienced two-fold greater success when attacking prey while submerged. These estimates are the first for wild adult American alligators and one of the few examples for any crocodilian species worldwide. More broadly, these results reveal that our understandings of crocodilian foraging behaviors are biased due to previous studies containing limited observations of cryptic and nocturnal foraging interactions. Our results can be used to inform greater understanding regarding the top-down effects of American alligators in estuarine food webs. Additionally, our results highlight the importance and power of using animal

  7. Steady state of active systems is characterized by unique effective temperature

    CERN Document Server

    Nandi, Saroj Kumar

    2016-01-01

    Understanding the properties of active matter systems, consisting of particles capable of taking up and dissipating energy and thus driven out of equilibrium, is important as it provides the possibility of a unified framework to analyze a diverse class of biological systems. Analysis of a large number of such systems shows an extension of equilibrium-like ideas are, sometimes, capable of capturing the steady state properties and a thermodynamic formulation of the problem might be possible. Investigating the detailed steady state properties and how the systems depart from equilibrium is important for such a formulation. Here we address the question through the framework of mode-coupling theory for dense active systems. We obtain a generic nonequilirbium theory for such systems and then taking the steady state limit of the theory we show that the system is characterized by a unique effective temperature, unlike other driven systems like a glass under shear. We discuss the differences of the steady states of an ...

  8. [Relationship among soil enzyme activities, vegetation state, and soil chemical properties of coal cinder yard].

    Science.gov (United States)

    Wang, Youbao; Zhang, Li; Liu, Dengyi

    2003-01-01

    From field investigation and laboratory analysis, the relationships among soil enzyme activities, vegetation state and soil chemical properties of coal cinder yard in thermal power station were studied. The results showed that vegetation on coal cinder yard was distributed in scattered patch mainly with single species of plant, and herbs were the dominant species. At the same time, the activity of three soil enzymes had a stronger relativity to environment conditions, such as vegetation state and soil chemical properties. The sensitivity of three soil enzymes to environmental stress was in order of urease > sucrase > catalase. The relativity of three soil enzymes to environmental factor was in order of sucrase > urease > catalase. Because of urease being the most susceptible enzyme to environmental conditions, and it was marked or utmost marked interrelated with vegetation state and soil chemical properties, urease activity could be used as an indicator for the reclamation of wasteland.

  9. Hidden State Conditional Random Field for Abnormal Activity Recognition in Smart Homes

    Directory of Open Access Journals (Sweden)

    Yu Tong

    2015-03-01

    Full Text Available As the number of elderly people has increased worldwide, there has been a surge of research into assistive technologies to provide them with better care by recognizing their normal and abnormal activities. However, existing abnormal activity recognition (AAR algorithms rarely consider sub-activity relations when recognizing abnormal activities. This paper presents an application of the Hidden State Conditional Random Field (HCRF method to detect and assess abnormal activities that often occur in elderly persons’ homes. Based on HCRF, this paper designs two AAR algorithms, and validates them by comparing them with a feature vector distance based algorithm in two experiments. The results demonstrate that the proposed algorithms favorably outperform the competitor, especially when abnormal activities have same sensor type and sensor number as normal activities.

  10. Predicting risk-taking behavior from prefrontal resting-state activity and personality.

    Directory of Open Access Journals (Sweden)

    Bettina Studer

    Full Text Available Risk-taking is subject to considerable individual differences. In the current study, we tested whether resting-state activity in the prefrontal cortex and trait sensitivity to reward and punishment can help predict risk-taking behavior. Prefrontal activity at rest was assessed in seventy healthy volunteers using electroencephalography, and compared to their choice behavior on an economic risk-taking task. The Behavioral Inhibition System/Behavioral Activation System scale was used to measure participants' trait sensitivity to reward and punishment. Our results confirmed both prefrontal resting-state activity and personality traits as sources of individual differences in risk-taking behavior. Right-left asymmetry in prefrontal activity and scores on the Behavioral Inhibition System scale, reflecting trait sensitivity to punishment, were correlated with the level of risk-taking on the task. We further discovered that scores on the Behavioral Inhibition System scale modulated the relationship between asymmetry in prefrontal resting-state activity and risk-taking. The results of this study demonstrate that heterogeneity in risk-taking behavior can be traced back to differences in the basic physiology of decision-makers' brains, and suggest that baseline prefrontal activity and personality traits might interplay in guiding risk-taking behavior.

  11. Coherent states of the Euclidean group and activation regions of primary visual cortex

    CERN Document Server

    Barbieri, Davide; Sanguinetti, Gonzalo; Sarti, Alessandro

    2011-01-01

    The uncertainty principle of SE(2) allows to construct a coherent states transform that is strictly related to the Bargmann transform for the second Heisenberg group H2. The corresponding target space is characterized constructively and related to the almost complex structure of SE(2) as a contact manifold. Such a coherent state transform provides a model for neural activity maps in the primary visual cortex, that are then described in terms of minimal uncertainty states. The results of the model are compared with the experimental measurements.

  12. Spin state transition in the active center of the hemoglobin molecule: DFT + DMFT study

    Science.gov (United States)

    Novoselov, D.; Korotin, Dm. M.; Anisimov, V. I.

    2016-05-01

    An ab initio study of electronic and spin configurations of the iron ion in the active center of the human hemoglobin molecule is presented. With a combination of the Density Functional Theory (DFT) method and the Dynamical Mean Field Theory (DMFT) approach, the spin state transition description in the iron ion during the oxidation process is significantly improved in comparison with previous attempts. It was found that the origin of the iron ion local moment behavior both for the high-spin and for the low-spin states in the hemoglobin molecule is caused by the presence of a mixture of several atomic states with comparable statistical probability.

  13. State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, D M; Poe, G R;

    1996-01-01

    Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached...... to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz...

  14. Dolphin changes in whistle structure with watercraft activity depends on their behavioral state.

    Science.gov (United States)

    May-Collado, Laura J; Quiñones-Lebrón, Shakira G

    2014-04-01

    Dolphins rely on whistles to identify each other and to receive and convey information about their environment. Although capable of adjusting these signals with changing environments, there is little information on how dolphins acoustically respond to different watercraft activities and if this response depends on dolphin behavioral state. Bottlenose dolphin whistles were recorded in the presence of research and dolphin-watching boats. Dolphins emitted lower frequency and longer whistles when interacting with dolphin-watching boats, particularly during foraging activities. This study suggests that dolphin-watching boat traffic significantly hinders dolphin communication during important behavioral states.

  15. Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme.

    Science.gov (United States)

    Pareek, Vidhi; Samanta, Moumita; Joshi, Niranjan V; Balaram, Hemalatha; Murthy, Mathur R N; Balaram, Padmanabhan

    2016-04-01

    Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.

  16. Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

    Science.gov (United States)

    Liu, Hai-Jing; Tang, Zhen-Xin; Han, Xue-Min; Yang, Zhi-Ling; Zhang, Fu-Min; Yang, Hai-Ling; Liu, Yan-Jing; Zeng, Qing-Yin

    2015-11-01

    Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

  17. On the role of thermal activation in selective photochemistry: mechanistic insight into the oxidation of propene on the V4O11- cluster.

    Science.gov (United States)

    Li, Shaohui; Demuth, Juri; Mirabal, Aldo; Wöste, Ludger; Siebert, Torsten

    2012-01-07

    An experimental methodology for a mechanistic analysis of gas phase chemical reactions is presented in the context of structure-reactivity relationships of metal oxide clusters relevant to photocatalysis. The spectroscopic approach is demonstrated with the investigation of the photoinduced oxygenation of propene on the V(4)O(11)(-) cluster, where the thermal activation and subsequent photoreaction are deduced with the information from (i) the temperature dependency of the aggregation kinetics in the propene-seeded helium atmosphere of an ion-trap reactor; (ii) the fluence dependency in the yield of different product channels of the photoreaction and (iii) the intensity dependency in the fragmentation of neutral reaction products that are probed via in situ multi-photon ionization. For the thermal reaction, selective hydrogen abstraction from the allylic position of propene accompanied by the linkage to the cluster at the dioxo moiety is postulated as the mechanism in the aggregation of propene on the V(4)O(11)(-) cluster. In accordance with an insightful neutralization-reionization study (Schröder et al., J. Mass. Spectrom., 2010, 301, 84), the subsequent photoinduced reaction is defined by an allylic oxidation in the formation of acrolein from the initial allyloxy radical photoproduct. The relevance of the observed selectivity is discussed in view of the electronic structure and bond motifs offered by high valence oxide systems such as the V(4)O(11)(-) cluster.

  18. Frontopolar activity and connectivity support dynamic conscious augmentation of creative state.

    Science.gov (United States)

    Green, Adam E; Cohen, Michael S; Raab, Hillary A; Yedibalian, Christopher G; Gray, Jeremy R

    2015-03-01

    No ability is more valued in the modern innovation-fueled economy than thinking creatively on demand, and the "thinking cap" capacity to augment state creativity (i.e., to try and succeed at thinking more creatively) is of broad importance for education and a rich mental life. Although brain-based creativity research has focused on static individual differences in trait creativity, less is known about changes in creative state within an individual. How does the brain augment state creativity when creative thinking is required? Can augmented creative state be consciously engaged and disengaged dynamically across time? Using a novel "thin slice" creativity paradigm in 55 fMRI participants performing verb-generation, we successfully cued large, conscious, short-duration increases in state creativity, indexed quantitatively by a measure of semantic distance derived via latent semantic analysis. A region of left frontopolar cortex, previously associated with creative integration of semantic information, exhibited increased activity and functional connectivity to anterior cingulate gyrus and right frontopolar cortex during cued augmentation of state creativity. Individual differences in the extent of increased activity in this region predicted individual differences in the extent to which participants were able to successfully augment state creative performance after accounting for trait creativity and intelligence.

  19. Insights from angle-resolved photoemission spectroscopy on the metallic states of YbB6(001): E(k) dispersion, temporal changes, and spatial variation

    NARCIS (Netherlands)

    Frantzeskakis, E.; de Jong, N.; Zhang, J.X.; Zhang, X.; Li, Z.; Liang, C.L.; Wang, Y.; Varykhalov, A.; Huang, Y.K.; Golden, M.S.

    2014-01-01

    We report high-resolution angle-resolved photoelectron spectroscopy (ARPES) results on the (001) cleavage surface of YbB6, a rare-earth compound that has been recently predicted to host surface electronic states with topological character. We observe two types of well-resolved metallic states, whose

  20. Extracellular potassium dynamics in the hyperexcitable state of the neuronal ictal activity

    Science.gov (United States)

    Florence, Gerson; Pereira, Tiago; Kurths, Jürgen

    2012-12-01

    An enduring question in epilepsy research concerns with the mechanisms responsible for the neuronal hyperexcitability. This theme is under debate and different hypotheses have been put forward. One hypothesis relates to extracellular ionic variations, especially the increase of the extracellular potassium concentration ([K+]o). During the epileptiform bursting, an increase of [K+]o is observed which raises the cellular excitability. It remains unclear, however, how the extracellular potassium variation could affect the generation and persistence of epileptiform bursting within the ictal phase, that is, during the epileptic seizure. The neuronal mechanisms responsible for this cellular hyperexcitability are not yet fully understood, hindering the development of more efficient therapies to control epilepsy. Mathematical models with biological plausibility have provided considerable insights into the mechanisms underlying epileptiform pattern. This paper reviews experimental evidences and computational studies concerning effects of the extracellular potassium dynamics on the cellular excitability within the neuronal ictal activity.

  1. Reduction in Cortical Gamma Synchrony during Depolarized State of Slow Wave Activity in Mice

    Directory of Open Access Journals (Sweden)

    EUNJIN eHWANG

    2013-12-01

    Full Text Available EEG gamma band oscillations have been proposed to account for the neural synchronization crucial for perceptual integration. While increased gamma power and synchronization is generally observed during cognitive tasks performed during wake, several studies have additionally reported increased gamma power during sleep or anesthesia, raising questions about the characteristics of gamma oscillation during impaired consciousness and its role in conscious processing. Phase-amplitude modulation has been observed between slow wave activity (SWA, 0.5–4 Hz and gamma oscillations during ketamine/xylazine anesthesia or sleep, showing increased gamma activity corresponding to the depolarized (ON state of SWA. Here we divided gamma activity into its ON and OFF (hyperpolarized state components based on the phase of SWA induced by ketamine/xylazine anesthesia and compared their power and synchrony with wake state levels in mice. We further investigated the state-dependent changes in both gamma power and synchrony across primary motor and primary somatosensory cortical regions and their interconnected thalamic regions throughout anesthesia and recovery. As observed previously, gamma power was as high as during wake specifically during the ON state of SWA. However, the synchrony of this gamma activity between somatosensory-motor cortical regions was significantly reduced compared to the baseline wake state. In addition, the somatosensory-motor cortical synchrony of gamma oscillations was reduced and restored in an anesthetic state-dependent manner, reflecting the changing depth of anesthesia. Our results provide evidence that during anesthesia changes in long-range information integration between cortical regions might be more critical for changes in consciousness than changes in local gamma oscillatory power.

  2. Bromine soil/sediment enrichment in tidal salt marshes as a potential indicator of climate changes driven by solar activity: New insights from W coast Portuguese estuaries.

    Science.gov (United States)

    Moreno, J; Fatela, F; Leorri, E; Moreno, F; Freitas, M C; Valente, T; Araújo, M F; Gómez-Navarro, J J; Guise, L; Blake, W H

    2017-02-15

    This paper aims at providing insight about bromine (Br) cycle in four Portuguese estuaries: Minho, Lima (in the NW coast) and Sado, Mira (in the SW coast). The focus is on their tidal marsh environments, quite distinct with regard to key biophysicochemical attributes. Regardless of the primary bromide (Br(-)) common natural source, i.e., seawater, the NW marshes present relatively higher surface soil/sediment Br concentrations than the ones from SW coast. This happens in close connection with organic matter (OM) content, and is controlled by their main climatic contexts. Yet, the anthropogenic impact on Br concentrations cannot be discarded. Regarding [Br] spatial patterns across the marshes, the results show a general increase from tidal flat toward high marsh. Maxima [Br] occur in the upper driftline zone, at transition from highest low marsh to high marsh, recognized as a privileged setting for OM accumulation. Based on the discovery of OM ubiquitous bromination in marine and transitional environments, it is assumed that this Br occurs mainly as organobromine. Analysis of two dated sediment cores indicates that, despite having the same age (AD ~1300), the Caminha salt marsh (Minho estuary) evidences higher Br enrichment than the Casa Branca salt marsh (Mira estuary). This is related to a greater Br storage ability, which is linked to OM build-up and rate dynamics under different climate scenarios. Both cores evidence a fairly similar temporal Br enrichment pattern, and may be interpreted in light of the sun-climate coupling. Thereby, most of the well-known Grand Solar Minima during the Little Ice Age appear to have left an imprint on these marshes, supported by higher [Br] in soils/sediments. Besides climate changes driven by solar activity and impacting marsh Br biogeodynamics, those Br enrichment peaks might also reflect inputs of enhanced volcanic activity covarying with Grand Solar Minima.

  3. Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.

    Science.gov (United States)

    Hu, Jianping; Feng, Zhiwei; Ma, Shifan; Zhang, Yu; Tong, Qin; Alqarni, Mohammed Hamed; Gou, Xiaojun; Xie, Xiang-Qun

    2016-06-27

    antagonist(s) at low concentration. Moreover, the hit from the active CB2 model also behaves as a neutral antagonist at low concentration. Our studies provide new insight leading to a better understanding of the structural and conformational differences between two states of CB2 and illuminate the effects of structure on virtual screening and drug design.

  4. Correlations in background activity control persistent state stability and allow execution of working memory tasks

    Directory of Open Access Journals (Sweden)

    Mario eDipoppa

    2013-10-01

    Full Text Available Working memory (WM is tightly capacity limited, it requires selective information gating, active information maintenance, and rapid active updating. Hence performing a WM task needs rapid and controlled transitions between neural persistent activity and the resting state. We propose that changes in spike-time correlations in neural activity provides a mechanism for the required working memory operations. As a proof of principle, we implement sustained activity and working memory in a recurrently-coupled spiking network with neurons receiving excitatory random background activity where background correlations are induced by a common noise source. We first characterize how the level of background correlations controls the stability of the persistent state. With sufficiently high correlations, the sustained state becomes practically unstable, so it cannot be initiated by a transient stimulus. We exploit this in a working memory model implementing the delay match to sample task by modulating flexibly in time the correlation level at different phases of the task. The modulation sets the network in different working regimes: more prompt to gate in a signal or clear the memory. The findings presented in this manuscript can form the basis for a new paradigm about how correlations are flexibly controlled by the cortical circuits to execute WM operations.

  5. An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

    Directory of Open Access Journals (Sweden)

    Marcello eCosta

    2013-04-01

    Full Text Available Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the ‘three-element model’ proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fibre-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap from diameter (DMap and pressure changes (PMaps. In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates ‘orbits’ that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans.

  6. Identification of resting and active state EEG features of Alzheimer's disease using discrete wavelet transform.

    Science.gov (United States)

    Ghorbanian, Parham; Devilbiss, David M; Verma, Ajay; Bernstein, Allan; Hess, Terry; Simon, Adam J; Ashrafiuon, Hashem

    2013-06-01

    Alzheimer's disease (AD) is associated with deficits in a number of cognitive processes and executive functions. Moreover, abnormalities in the electroencephalogram (EEG) power spectrum develop with the progression of AD. These features have been traditionally characterized with montage recordings and conventional spectral analysis during resting eyes-closed and resting eyes-open (EO) conditions. In this study, we introduce a single lead dry electrode EEG device which was employed on AD and control subjects during resting and activated battery of cognitive and sensory tasks such as Paced Auditory Serial Addition Test (PASAT) and auditory stimulations. EEG signals were recorded over the left prefrontal cortex (Fp1) from each subject. EEG signals were decomposed into sub-bands approximately corresponding to the major brain frequency bands using several different discrete wavelet transforms and developed statistical features for each band. Decision tree algorithms along with univariate and multivariate statistical analysis were used to identify the most predictive features across resting and active states, separately and collectively. During resting state recordings, we found that the AD patients exhibited elevated D4 (~4-8 Hz) mean power in EO state as their most distinctive feature. During the active states, however, the majority of AD patients exhibited larger minimum D3 (~8-12 Hz) values during auditory stimulation (18 Hz) combined with increased kurtosis of D5 (~2-4 Hz) during PASAT with 2 s interval. When analyzed using EEG recording data across all tasks, the most predictive AD patient features were a combination of the first two feature sets. However, the dominant discriminating feature for the majority of AD patients were still the same features as the active state analysis. The results from this small sample size pilot study indicate that although EEG recordings during resting conditions are able to differentiate AD from control subjects, EEG activity

  7. Glucocorticoid-induced impairment of macrophage antimicrobial activity: mechanisms and dependence on the state of activation.

    Science.gov (United States)

    Schaffner, A; Schaffner, T

    1987-01-01

    Experimental observations indicate that tissue macrophages deployed in great numbers at critical anatomic sites such as the liver, spleen, and lung are major targets for glucocorticoids compromising natural resistance of the host. Therapeutic concentrations of glucocorticoids appear to prevent destruction of microorganisms ingested by macrophages without interfering with phagocytosis, phagolysosomal fusion, and/or secretion of reactive oxygen intermediates. These findings indicate that at the cellular level the glucocorticoid target should be sought for in the nonoxidative armature of the phagocyte and that nonoxidative killing systems of resident tissue macrophages play an important role in natural resistance to opportunistic pathogens. Glucocorticoids do not prevent lymphokine-induced activation of oxidative killing systems. Thus, lymphokines such as interferon-gamma can restore the microbicidal activity of macrophages functionally impaired by glucocorticoids. Counterbalance of the suppressive effect of glucocorticoids by lymphokines might only be possible, however, for pathogens susceptible to oxidative killing and not for microorganisms that are more resistant to reactive oxygen intermediates such as Aspergillus spores and Nocardia, opportunists that appear to be particularly associated with hypercortisolism.

  8. Inadequate physical activity and health care expenditures in the United States.

    Science.gov (United States)

    Carlson, Susan A; Fulton, Janet E; Pratt, Michael; Yang, Zhou; Adams, E Kathleen

    2015-01-01

    This study estimates the percentage of health care expenditures in the non-institutionalized United States (U.S.) adult population associated with levels of physical activity inadequate to meet current guidelines. Leisure-time physical activity data from the National Health Interview Survey (2004-2010) were merged with health care expenditure data from the Medical Expenditure Panel Survey (2006-2011). Health care expenditures for inactive (i.e., no physical activity) and insufficiently active adults (i.e., some physical activity but not enough to meet guidelines) were compared with active adults (i.e., ≥150minutes/week moderate-intensity equivalent activity) using an econometric model. Overall, 11.1% (95% CI: 7.3, 14.9) of aggregate health care expenditures were associated with inadequate physical activity (i.e., inactive and insufficiently active levels). When adults with any reported difficulty walking due to a health problem were excluded, 8.7% (95% CI: 5.2, 12.3) of aggregate health care expenditures were associated with inadequate physical activity. Increasing adults' physical activity to meet guidelines may reduce U.S. health care expenditures.

  9. Tristable and multiple bistable activity in complex random binary networks of two-state units

    CERN Document Server

    Christ, Simon; Schimansky-Geier, Lutz

    2016-01-01

    We study complex networks of stochastic two-state units. Our aim is to model discrete stochastic excitable dynamics with a rest and an excited state. These two states are assumed to possess different waiting time distributions. The rest state is treated as an activation process with an exponentially distributed life time, whereas the latter in the excited state shall have a constant mean which may originate from any distribution. The activation rate of any single unit is determined by its neighbors according to a random complex network structure. In order to treat this problem in an analytical way, we use a heterogeneous mean-field approximation yielding a set of equations general valid for uncorrelated random networks. Based on this derivation we focus on random binary networks where the network is solely comprised of nodes with either of two degrees. The ratio between the two degrees is shown to be a crucial parameter. Dependent on the composition of the network the steady states show the usual transition f...

  10. TUNL XIX. Annual report, January 1-December 31, 1980. [North Carolina State Univ. activities at TUNL

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-12-31

    Research performed by North Carolina State University personnel at TUNL is highlighted in this report, which is actually the complete TUNL progress report for 1980. Studies in the areas of neutron cross sections, neutron polarization, radiative capture, atomic physics and development activities are included. One may expect completed projects to be reported in physics journals or conference proceedings. (RWR)

  11. 75 FR 27575 - Agency Information Collection Activities: State Water Resources Research Institute Program Annual...

    Science.gov (United States)

    2010-05-17

    ... Geological Survey Agency Information Collection Activities: State Water Resources Research Institute Program... notifying the public that we have submitted to the Office of Management and Budget (OMB) an information... collection of information unless it displays a currently valid OMB control number. DATES: You must...

  12. 78 FR 46597 - Agency Information Collection Activities: State Water Resources Research Institute Program Annual...

    Science.gov (United States)

    2013-08-01

    ....S. Geological Survey Agency Information Collection Activities: State Water Resources Research...: Notice of an extension of currently approved information Collection, 1028-0097. SUMMARY: To comply with... an information collection request (ICR) that we have sent to the Office of Management and Budget...

  13. Participation of Elderly Women in Community Welfare Activities in Akinyele Local Government, Oyo State, Nigeria

    Science.gov (United States)

    Odebode, Stella O.

    2009-01-01

    This paper assessed the participation of elderly women in community welfare activities in Oyo State, Nigeria. Simple random sampling technique was used to select 120 elderly women from six out of the twelve political wards in the study area. Both qualitative and quantitative methods of data collection were used to elicit information from the…

  14. Temporal pole activity during understanding other persons' mental states correlates with neuroticism trait.

    Science.gov (United States)

    Jimura, Koji; Konishi, Seiki; Asari, Tomoki; Miyashita, Yasushi

    2010-04-30

    Comprehension of other persons' mental states is one of the representative cognitive functions involved in social situations. It has been suggested that this function sometimes recruits emotional processes. The present fMRI study examined the neural mechanisms associated with understanding others' mental states, and the conditions that determine the recruitment of the emotional processes. The false belief paradigm, a traditional behavioral paradigm to investigate comprehension of others, was applied to an event-related fMRI analysis, allowing for the extraction of brain activity time-locked to successful understanding of others' mental states. Prominent brain activity was observed in multiple cortical regions including the medial prefrontal cortex, temporo-parietal junction, precuneus, and temporal pole. Then, correlational analyses were performed between the activations and individuals' scores of neuroticism, a personality trait that reflects emotional instability in daily life. It was revealed that the neuroticism scores were positively correlated with the activity in the temporal pole region, but not in the other regions. These results suggest that the emotional processes implemented in the temporal pole are recruited during successful understanding of other persons' mental states, and that the recruitment may be modulated by an emotional personality trait of individual subjects.

  15. 78 FR 22251 - Agency Information Collection Activities; Comment Request; IDEA Part B State Performance Plan...

    Science.gov (United States)

    2013-04-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Comment Request; IDEA Part B State Performance Plan (SPP) and... in response to this notice will be considered public records. Title of Collection: IDEA Part B...

  16. 78 FR 22253 - Agency Information Collection Activities; Comment Request; IDEA Part C State Performance Plan...

    Science.gov (United States)

    2013-04-15

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF EDUCATION Agency Information Collection Activities; Comment Request; IDEA Part C State Performance Plan (SPP) and... in response to this notice will be considered public records. Title of Collection: IDEA Part C...

  17. Participation, responsibility and choice: summoning the active citizen in Western European welfare states

    NARCIS (Netherlands)

    Newman, J.; Tonkens, E.

    2011-01-01

    Responsibility, participation and choice are key policy framings of active citizenship, summoning the citizen to take on new roles in welfare state reform. This volume traces the emergence of new discourses and the ways in which they take up and rework struggles of social movements for greater indep

  18. 78 FR 5793 - Agency Information Collection Activities; Comment Request; Evaluation of State Expanded Learning...

    Science.gov (United States)

    2013-01-28

    ... Agency Information Collection Activities; Comment Request; Evaluation of State Expanded Learning Time... Reduction Act of 1995 (44 U.S.C. chapter 3501 et seq.), ED is proposing a new information collection. DATES... submitted after the comment period will not be accepted. Written requests for information or...

  19. Teen Sexual Activity, Pregnancy and Childbearing among Latinos in the United States. Fact Sheet.

    Science.gov (United States)

    National Campaign To Prevent Teen Pregnancy, Washington, DC.

    The Latino population is the fastest-growing major racial/ethnic group in the United States. By 2020, approximately 16 percent of the population will be Latino. This increase will be even more pronounced among teens. This fact sheet summarizes data from the National Vital Statistics Reports on reported sexual activity, pregnancy rates, and…

  20. Association and Diffusion of Nutrition and Physical Activity Policies on the State and District Level

    Science.gov (United States)

    Taber, Daniel R.; Chriqui, Jamie F.; Chaloupka, Frank J.

    2012-01-01

    Background: School district wellness policies designed to reduce obesity and promote student health and well-being often lack specific requirements or any mandate that schools comply with the policy. Researchers, educators, and policymakers have called for states to take an active role in shaping district policies. The objective of this study was…

  1. 12 CFR 347.116 - Recordkeeping and supervision of foreign activities of insured state nonmember banks.

    Science.gov (United States)

    2010-01-01

    ... volatility. Information should be available on sources of liquidity—cash, balances with banks, marketable... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Recordkeeping and supervision of foreign activities of insured state nonmember banks. 347.116 Section 347.116 Banks and Banking FEDERAL...

  2. Visualization of the Differential Transition State Stabilization within the Active Site Environment

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski

    2004-05-01

    Full Text Available Abstract: Increasing interest in the enzymatic reaction mechanisms and in the nature of catalytic effects in enzymes causes the need of appropriate visualization methods. A new interactive method to investigate catalytic effects using differential transition state stabilization approach (DTSS [1, 2] is presented. The catalytic properties of the active site of cytidine deaminase (E.C. 3.5.4.5 is visualized in the form of differential electrostatic properties. The visualization was implemented using scripting interface of VMD [3]. Cumulative Atomic Multipole Moments (CAMM [4,5,6] were utilized for efficient yet accurate evaluation of the electrostatic properties. The implementation is efficient enough for interactive presentation of catalytic effects in the active site of the enzyme due to transition state or substrate movement. This system of visualization of DTTS approach can be potentially used to validate hypotheses regarding the catalytic mechanism or to study binding properties of transition state analogues.

  3. An Old Story in New Light: X-Ray Powder Diffraction Provides Novel Insights into a Long-Known Organic Solid-State Rearrangement Reaction

    OpenAIRE

    Halasz, Ivan; Cindro, Nikola; Dinnebier, Robert E; Vančik, Hrvoj

    2013-01-01

    The first in situ diffraction study of the long-known solid-state rearrangement of p-bromobenzeneazotribenzoylmethane is reported. This proof-of-principle study demonstrates how modern laboratory X-ray powder diffraction, accompanied by up-to-date processing tools, can be used to monitor and describe mechanisms of organic solid-state reactions while it also underpins its necessity for structural characterisation of in situ formed crystalline phases. (doi: 10.5562/cca2127)

  4. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.

    Science.gov (United States)

    Palhano-Fontes, Fernanda; Andrade, Katia C; Tofoli, Luis F; Santos, Antonio C; Crippa, Jose Alexandre S; Hallak, Jaime E C; Ribeiro, Sidarta; de Araujo, Draulio B

    2015-01-01

    The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

  5. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.

    Directory of Open Access Journals (Sweden)

    Fernanda Palhano-Fontes

    Full Text Available The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN, a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN. Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC/Precuneus and the medial Prefrontal Cortex (mPFC. Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic, meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

  6. PRE-AND POST-ACTIVITY STRETCHING PRACTICES OF COLLEGIATE ATHLETIC TRAINERS IN THE UNITED STATES.

    Science.gov (United States)

    Popp, Jennifer K; Bellar, David; Hoover, Donald L; Craig, Bruce W; Leitzelar, Brianna N; Wanless, Elizabeth A; Judge, Lawrence W

    2015-02-14

    The aim of the study was to investigate the knowledge and practices of collegiate-certified athletic trainers (ATs) in the United States. Participants (n= 521) were provided an overview of the study, as well as a hyperlink to a web-based survey. The "Pre- and Post-Activity Practices in Athletic Training Questionnaire" consisted of demographic items and elements to measure knowledge and practices related to pre- and post-activity stretching routines. In previous studies, the survey demonstrated construct validity, α = .722. Pearson chi-square test was used to evaluate goodness of fit, and kappa was calculated to measure agreement between items. Only 32.2% of ATs recommended dynamic stretching (DS) to be performed pre-activity, whereas a larger percentage (42.2%) recommended a combination of static stretching (SS) and DS. ATs reported that only 28.0% of athletes are performing DS prior to activity. Conversely, 60.6% of collegiate ATs recommended SS post-exercise, and 61.0% of athletes agree and perform post-workout static stretching (κ=0.761, P<0.001). Collegiate ATs appear to under-utilize the current research evidence, which indicates that DS is more beneficial than SS when used pre-activity, and ATs continue to regularly incorporate SS in their pre-activity routines. However, there is evidence that collegiate ATs in the United States emphasize SS post-activity in a manner consistent with current research.

  7. Insights into the 2011-2012 submarine eruption off the coast of El Hierro (Canary Islands, Spain) from statistical analyses of earthquake activity

    Science.gov (United States)

    Ibáñez, J. M.; De Angelis, S.; Díaz-Moreno, A.; Hernández, P.; Alguacil, G.; Posadas, A.; Pérez, N.

    2012-08-01

    The purpose of this work is to gain insights into the 2011-2012 eruption of El Hierro (Canary Islands) by mapping the evolution of the seismic b-value. The El Hierro seismic sequence offers a rather unique opportunity to investigate the process of reawakening of an oceanic intraplate volcano after a long period of repose. The 2011-2012 eruption is a submarine volcanic event that took place about 2 km off of the southern coast of El Hierro. The eruption was accompanied by an intense seismic swarm and surface manifestations of activity. The earthquake catalogue during the period of unrest includes over 12 000 events, the largest with magnitude 4.6. The seismic sequence can be grouped into three distinct phases, which correspond to well-separated spatial clusters and distinct earthquake regimes. The estimated b-value is of 1.18 ± 0.03, and a magnitude of completeness of 1.3, for the entire catalogue. B is very close to 1.0, which indicates completeness of the earthquake catalogue with only minor departures from the linearity of Gutenberg-Richter frequency-magnitude distribution. The most straightforward interpretation of this result is that the seismic swarm reached its final stages, and no additional large magnitude events should be anticipated, similarly to what one would expect for non-volcanic earthquake sequences. The results, dividing the activity in different phases, illustrate remarkable differences in the estimate of b-value during the early and late stages of the eruption. The early pre-eruptive activity was characterized by a b-value of 2.25. In contrast, the b-value was 1.25 during the eruptive phase. Based on our analyses, and the results of other studies, we propose a scenario that may account for the observations reported in this work. We infer that the earthquakes that occurred in the first phase reflect magma migration from the upper mantle to crustal depths. The area where magma initially intruded into the crust, because of its transitional nature

  8. Transport dynamics of molecular motors that switch between an active and inactive state.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  9. In Vitro Activity of Delafloxacin against Contemporary Bacterial Pathogens from the United States and Europe, 2014

    Science.gov (United States)

    Pfaller, M. A.; Sader, H. S.; Rhomberg, P. R.

    2017-01-01

    ABSTRACT The in vitro activities of delafloxacin and comparator antimicrobial agents against 6,485 bacterial isolates collected from medical centers in Europe and the United States in 2014 were tested. Delafloxacin was the most potent agent tested against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus, Streptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci and had activity similar to that of ciprofloxacin and levofloxacin against certain members of the Enterobacteriaceae. Overall, the broadest coverage of the tested pathogens (Gram-positive cocci and Gram-negative bacilli) was observed with meropenem and tigecycline in both Europe and the United States. Delafloxacin was shown to be active against organisms that may be encountered in acute bacterial skin and skin structure infections, respiratory infections, and urinary tract infections. PMID:28167542

  10. The Relationship Between Beta Endorphins and Emotional State in Physically Active Individuals Aged 45-55 (A Report on a Pilot Study

    Directory of Open Access Journals (Sweden)

    Kundziņa Ieva

    2014-09-01

    Full Text Available Introduction. This sports-science-related article heavily relies on studies that have reported an increase in beta-endorphin (â-EP concentration in plasma in response to physical activity. It examines the psychological and physiological effects of physical activity and exercise and reports on a research-experiment-based, endorphin-hypotheses-related pilot study aimed at exploring mood-related â-EP effects occurring in physically active male and female individuals aged 45-55 in response to physical load. Material and methods. Six 45 to 55-year-old individuals (3 males and 3 females rated as exhibiting moderate and high levels of physical activity in sport's laboratory. International Physical Activity Questionnaire (IPAQ was used to establish physical activity level. For facial expression analysis a short interview was applied, using software “FaceReader 3.0” (FR. As a load test a veloergometer exercise test was used, and Beta-endorphin (â-EP levels were measured from venous blood. Results. The findings demonstrated an increase in â-EP levels in 50% of the subjects. No positive relation between â-EP increase and happiness has been observed. In four subjects an increase in disgust was observed due to the laboratory conditions. Five minutes after the load test FR data recorded the reduction or disappearance of negative emotions for all research subjects. Conclusions. Further investigation into the relationship of plasma levels of â-EP and the emotional state of the individual involved in physical activities is needed. This necessitates a further insight into how exercise-elevated endorphins (â-EP affect mood state outside laboratory conditions. Therefore, a further investigation of people involved in physical recreation activities outdoors is envisaged.

  11. Motivational states activate distinct hippocampal representations to guide goal-directed behaviors.

    Science.gov (United States)

    Kennedy, Pamela J; Shapiro, Matthew L

    2009-06-30

    Adaptive behaviors are guided by motivation and memory. Motivational states specify goals, and memory can inform motivated behavior by providing detailed records of past experiences when goals were obtained. These 2 fundamental processes interact to guide animals to biologically relevant targets, but the neuronal mechanisms that integrate them remain unknown. To investigate these mechanisms, we recorded unit activity from the same population of hippocampal neurons as rats performed identical tasks while either food or water deprived. We compared the influence of motivational state (hunger and thirst), memory demand, and spatial behavior in 2 tasks: hippocampus-dependent contextual memory retrieval and hippocampus-independent random foraging. We found that: (i) hippocampal coding was most strongly influenced by motivational state during contextual memory retrieval, when motivational cues were required to select among remembered, goal-directed actions in the same places; (ii) the same neuronal populations were relatively unaffected by motivational state during random foraging, when hunger and thirst were incidental to behavior, and signals derived from deprivation states thus informed, but did not determine, hippocampal coding; and (iii) "prospective coding" in the contextual retrieval task was not influenced by allocentric spatial trajectory, but rather by the animal's deprivation state and the associated, non-spatial target, suggesting that hippocampal coding includes a wide range of predictive associations. The results show that beyond coding spatiotemporal context, hippocampal representations encode the relationships between internal states, the external environment, and action to provide a mechanism by which motivation and memory are coordinated to guide behavior.

  12. Activities Contributing to Total Energy Expenditure in the United States: Results from the NHAPS Study

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    Block Gladys

    2004-02-01

    Full Text Available Abstract Background Physical activity is increasingly recognized as an important factor influencing health and disease status. Total energy expenditure, both low-intensity and high-intensity, contributes to maintenance of healthy body weight. This paper presents the results of a quantitative approach to determining the activities that contribute to total energy expenditure in the United States. Methods Data from the National Human Activity Pattern Survey (NHAPS were used. In 1992–1994 the NHAPS sampled 4,185 females and 3,330 males, aged 18 years and over, weighted to be representative of the 48 contiguous United States. A detailed report of each activity performed in the previous 24 hours was obtained. A score was created for each activity, by multiplying duration and intensity for each individual and summing across individuals. This score was then used to rank each activity according to its contribution to total population energy expenditure, for the total sample and separately for each gender, race, age, region, and season. Results This analysis reveals our society to be primarily sedentary; leisure time physical activity contributed only approximately 5% of the population's total energy expenditure. Not counting sleeping, the largest contributor to energy expenditure was "Driving a car", followed by "Office work" and "Watching TV". Household activities accounted for 20.1% and 33.3% of energy expenditure for males and females respectively. Conclusion The information presented in this paper may be useful in identifying common activities that could be appropriate targets for behavioral interventions to increase physical activity.

  13. Translating Scientific Judgment, Technological Insight and Economic Theory Into Practical Policy Lessons: The Case of Climate Regulation in the United States

    Science.gov (United States)

    Mignone, B. K.

    2008-12-01

    Effective solutions to the climate change problem will require unprecedented cooperation across space, continuity across time and coordination between disciplines. One well-known methodology for synthesizing the lessons of physical science, energy engineering and economics is integrated assessment. Typically, integrated assessment models use scientific and technological relationships as physical constraints in a larger macroeconomic optimization that is designed to either balance the costs and benefits of climate change mitigation or find the least-cost path to an exogenously prescribed endpoint (e.g. atmospheric CO2 stabilization). The usefulness of these models depends to a large extent on the quality of the assumptions and the relevance of the outcome metrics chosen by the user. In this study, I show how a scientifically-based emissions reduction scenario can be combined with engineering-based assumptions about the energy system (e.g. estimates of the marginal cost premium of carbon-free technology) to yield insights about the price path of CO2 under a future regulatory regime. I then show how this outcome metric (carbon price) relates to key decisions about the design of a future cap-and-trade system and the way in which future carbon markets may be regulated.

  14. Predicting flow at work: investigating the activities and job characteristics that predict flow states at work.

    Science.gov (United States)

    Nielsen, Karina; Cleal, Bryan

    2010-04-01

    Flow (a state of consciousness where people become totally immersed in an activity and enjoy it intensely) has been identified as a desirable state with positive effects for employee well-being and innovation at work. Flow has been studied using both questionnaires and Experience Sampling Method (ESM). In this study, we used a newly developed 9-item flow scale in an ESM study combined with a questionnaire to examine the predictors of flow at two levels: the activities (brainstorming, planning, problem solving and evaluation) associated with transient flow states and the more stable job characteristics (role clarity, influence and cognitive demands). Participants were 58 line managers from two companies in Denmark; a private accountancy firm and a public elder care organization. We found that line managers in elder care experienced flow more often than accountancy line managers, and activities such as planning, problem solving, and evaluation predicted transient flow states. The more stable job characteristics included in this study were not, however, found to predict flow at work.

  15. Prevalence of Physical Activity in the United States: Behavioral Risk Factor Surveillance System, 2001

    Directory of Open Access Journals (Sweden)

    Barbara E. Ainsworth, PhD, MPH

    2005-03-01

    Full Text Available Introduction The health benefits of regular cardiovascular exercise are well-known. Such exercise, however, has traditionally been defined as vigorous physical activity, such as jogging, swimming, or aerobic dance. Exercise of moderate intensity also promotes health, and many U.S. adults may be experiencing the health benefits of exercise through lifestyle activities of moderate intensity, such as yard work, housework, or walking for transportation. Until recently, public health surveillance systems have not included assessments of this type of physical activity, focusing on exercise of vigorous intensity. We used an enhanced surveillance tool to describe the prevalence and amount of both moderate-intensity and vigorous-intensity physical activity among U.S. adults. Methods We analyzed data from the 2001 Behavioral Risk Factor Surveillance System, a state-based, random-digit–dialed telephone survey administered to U.S. adults aged 18 years and older (n = 82,834 men and 120,286 women. Physical activity behavior was assessed using questions designed to quantify the frequency of participation in moderate- or vigorous-intensity physical activities performed during leisure time or for household chores and transportation. Results Overall, 45% of adults (48% of men and 43% of women were active at recommended levels during nonworking hours (at least 30 minutes five or more days per week in moderate-intensity activities, equivalent to brisk walking, or at least 20 minutes three or more days per week in vigorous activities, equivalent to running, heavy yard work, or aerobic dance. Less than 16% of adults (15% of men and 17% of women reported no moderate or vigorous activity in a usual week. Conclusion Integrating surveillance of lifestyle activities into national systems is possible, and doing so may provide a more accurate representation of the prevalence of recommended levels of physical activity. These results, however, suggest that the majority of U

  16. Evaluation of behavioral states among morning and evening active healthy individuals

    Directory of Open Access Journals (Sweden)

    M.P. Hidalgo

    2002-07-01

    Full Text Available The Horne-Östberg questionnaire partly covers some factors that may be important determinants of peak time and characterize patterns of behavior. We conducted a study for the evaluation of self-reported behavioral states (hunger sensation, availability for study, physical exercise, solving daily problems, and time preferences as expressions of underlying cyclic activity. Three hundred and eighteen community subjects without history of medical, psychiatric, or sleep disorders were evaluated in a cross-sectional design. A self-report about daily highest level of activity was used to categorize individuals into morning, evening, and indifferently active. Time-related behavioral states were evaluated with 23 visual analog questions. The responses to most analogic questions were significantly different between morning and evening active subjects. Logistic regression analysis identified a group of behaviors more strongly associated with the self-reported activity pattern (common wake up time, highest subjective fatigue, as well as wake up, bedtime, exercise and study preferences. These findings suggested that the patterns of activity presented by normal adults were related to specific common behavioral characteristics that may contribute to peak time.

  17. Engineering electrocatalytic activity in nanosized perovskite cobaltite through surface spin-state transition

    Science.gov (United States)

    Zhou, Shiming; Miao, Xianbing; Zhao, Xu; Ma, Chao; Qiu, Yuhao; Hu, Zhenpeng; Zhao, Jiyin; Shi, Lei; Zeng, Jie

    2016-05-01

    The activity of electrocatalysts exhibits a strongly dependence on their electronic structures. Specifically, for perovskite oxides, Shao-Horn and co-workers have reported a correlation between the oxygen evolution reaction activity and the eg orbital occupation of transition-metal ions, which provides guidelines for the design of highly active catalysts. Here we demonstrate a facile method to engineer the eg filling of perovskite cobaltite LaCoO3 for improving the oxygen evolution reaction activity. By reducing the particle size to ~80 nm, the eg filling of cobalt ions is successfully increased from unity to near the optimal configuration of 1.2 expected by Shao-Horn's principle. Consequently, the activity is significantly enhanced, comparable to those of recently reported cobalt oxides with eg~1.2 configurations. This enhancement is ascribed to the emergence of spin-state transition from low-spin to high-spin states for cobalt ions at the surface of the nanoparticles, leading to more active sites with increased reactivity.

  18. Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

    Science.gov (United States)

    Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

    1990-11-01

    Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

  19. States and the (Not So) New Standards--Where Are They Now? State Academic Standards: Activity around the Common Core

    Science.gov (United States)

    Salazar, Tonette; Christie, Kathy

    2014-01-01

    States began adopting the Common Core State Standards (CCSS) in 2010 after they were launched by the Council of Chief State School Officers and the National Governors Association. Five years later, policymakers in numerous states continue to debate the Common Core and related elements, such as how to assess the standards. This brief provides a…

  20. Excited state absorption in glasses activated with rare earth ions: Experiment and modeling

    Science.gov (United States)

    Piatkowski, Dawid; Mackowski, Sebastian

    2012-10-01

    We present semiempirical approach based on the Judd-Ofelt theory and apply it for modeling the spectral properties of fluoride glasses activated with the rare earth (RE) ions. This method provide a powerful tool for simulating both ground state absorption (GSA) and excited state absorption (ESA) spectra of RE ions, e.g. Nd3+, Ho3+, Er3+ and Tm3+ in the ZBLAN glass matrix. The results of theoretical calculations correspond to the experimentally measured data. We also demonstrate that the spectra obtained using the presented approach are applicable in the analysis of up-conversion excitation schemes in these optoelectronically relevant materials.

  1. A Semi-Continuous State-Transition Probability HMM-Based Voice Activity Detector

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    H. Othman

    2007-02-01

    Full Text Available We introduce an efficient hidden Markov model-based voice activity detection (VAD algorithm with time-variant state-transition probabilities in the underlying Markov chain. The transition probabilities vary in an exponential charge/discharge scheme and are softly merged with state conditional likelihood into a final VAD decision. Working in the domain of ITU-T G.729 parameters, with no additional cost for feature extraction, the proposed algorithm significantly outperforms G.729 Annex B VAD while providing a balanced tradeoff between clipping and false detection errors. The performance compares very favorably with the adaptive multirate VAD, option 2 (AMR2.

  2. A Semi-Continuous State-Transition Probability HMM-Based Voice Activity Detector

    Directory of Open Access Journals (Sweden)

    Othman H

    2007-01-01

    Full Text Available We introduce an efficient hidden Markov model-based voice activity detection (VAD algorithm with time-variant state-transition probabilities in the underlying Markov chain. The transition probabilities vary in an exponential charge/discharge scheme and are softly merged with state conditional likelihood into a final VAD decision. Working in the domain of ITU-T G.729 parameters, with no additional cost for feature extraction, the proposed algorithm significantly outperforms G.729 Annex B VAD while providing a balanced tradeoff between clipping and false detection errors. The performance compares very favorably with the adaptive multirate VAD, option 2 (AMR2.

  3. Islands and the offshoring possibilities and strategies of contemporary states: insights on/for the migration phenomenon on Europe’s southern flank

    Directory of Open Access Journals (Sweden)

    Godfrey Baldacchino

    2014-05-01

    Full Text Available Islands have transitioned from being conceived as prototypes of idealised polities to being deliberately engineered as offshore enclaves where the rules of the parent state need not fully apply. With their manageable size, separation and distance from the mainland, small islands are rendered as convenient laboratories for entrepreneurial political engineering, and equally handy sites for research on the same. Island migration policies manifest this contemporary flexibility and creative governance of states. As we approach the 500th anniversary of Thomas More’s Utopia (1516, this paper explores these ideas in relation to the migration phenomenon on Europe’s southern flank. Using an island studies approach, it discusses the problematique of island spaces caught in this dynamic but which cannot be ‘offshore’ because, as unitary island states (Cyprus and Malta and unlike larger states with small outlying and peripheral island components (Italy and Australia, they must somehow be ‘both inside and outside’. The paper goes on to critique such facile binarisms, arguing for a more nuanced appreciation of islands as well as a recognition that what may be, at face value, an expression of a state’s authority is as much a manifestation of its limitations.

  4. Hurricane intensification along United States coast suppressed during active hurricane periods.

    Science.gov (United States)

    Kossin, James P

    2017-01-19

    The North Atlantic ocean/atmosphere environment exhibits pronounced interdecadal variability that is known to strongly modulate Atlantic hurricane activity. Variability in sea surface temperature (SST) is correlated with hurricane variability through its relationship with the genesis and thermodynamic potential intensity of hurricanes. Another key factor that governs the genesis and intensity of hurricanes is ambient environmental vertical wind shear (VWS). Warmer SSTs generally correlate with more frequent genesis and greater potential intensity, while VWS inhibits genesis and prevents any hurricanes that do form from reaching their potential intensity. When averaged over the main hurricane-development region in the Atlantic, SST and VWS co-vary inversely, so that the two factors act in concert to either enhance or inhibit basin-wide hurricane activity. Here I show, however, that conditions conducive to greater basin-wide Atlantic hurricane activity occur together with conditions for more probable weakening of hurricanes near the United States coast. Thus, the VWS and SST form a protective barrier along the United States coast during periods of heightened basin-wide hurricane activity. Conversely, during the most-recent period of basin-wide quiescence, hurricanes (and particularly major hurricanes) near the United States coast, although substantially less frequent, exhibited much greater variability in their rate of intensification, and were much more likely to intensify rapidly. Such heightened variability poses greater challenges to operational forecasting and, consequently, greater coastal risk during hurricane events.

  5. Decoding the Interactions Regulating the Active State Mechanics of Eukaryotic Protein Kinases.

    Science.gov (United States)

    Meharena, Hiruy S; Fan, Xiaorui; Ahuja, Lalima G; Keshwani, Malik M; McClendon, Christopher L; Chen, Angela M; Adams, Joseph A; Taylor, Susan S

    2016-11-01

    Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. In the active state, the catalytic core oscillates between open, intermediate, and closed conformations. Currently, the intramolecular interactions that regulate the active state mechanics are not well understood. Here, using cAMP-dependent protein kinase as a representative model coupled with biochemical, biophysical, and computational techniques, we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. These include the previously identified salt bridge between a lysine from the β3-strand and a glutamate from the αC-helix as well as an electrostatic interaction between the phosphorylated activation loop and αC-helix and an ensemble of hydrophobic residues of the Regulatory spine and Shell. Moreover, for over three decades it was thought that the highly conserved β3-lysine was essential for phosphoryl transfer, but our findings show that the β3-lysine is not required for phosphoryl transfer but is essential for the active state mechanics.

  6. Hurricane intensification along United States coast suppressed during active hurricane periods

    Science.gov (United States)

    Kossin, James P.

    2017-01-01

    The North Atlantic ocean/atmosphere environment exhibits pronounced interdecadal variability that is known to strongly modulate Atlantic hurricane activity. Variability in sea surface temperature (SST) is correlated with hurricane variability through its relationship with the genesis and thermodynamic potential intensity of hurricanes. Another key factor that governs the genesis and intensity of hurricanes is ambient environmental vertical wind shear (VWS). Warmer SSTs generally correlate with more frequent genesis and greater potential intensity, while VWS inhibits genesis and prevents any hurricanes that do form from reaching their potential intensity. When averaged over the main hurricane-development region in the Atlantic, SST and VWS co-vary inversely, so that the two factors act in concert to either enhance or inhibit basin-wide hurricane activity. Here I show, however, that conditions conducive to greater basin-wide Atlantic hurricane activity occur together with conditions for more probable weakening of hurricanes near the United States coast. Thus, the VWS and SST form a protective barrier along the United States coast during periods of heightened basin-wide hurricane activity. Conversely, during the most-recent period of basin-wide quiescence, hurricanes (and particularly major hurricanes) near the United States coast, although substantially less frequent, exhibited much greater variability in their rate of intensification, and were much more likely to intensify rapidly. Such heightened variability poses greater challenges to operational forecasting and, consequently, greater coastal risk during hurricane events.

  7. Ground state destabilization by anionic nucleophiles contributes to the activity of phosphoryl transfer enzymes.

    Directory of Open Access Journals (Sweden)

    Logan D Andrews

    2013-07-01

    Full Text Available Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 10²²-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound P(i was determined from pH dependencies of the binding of Pi and tungstate, a P(i analog lacking titratable protons over the pH range of 5-11, and from the ³¹P chemical shift of bound P(i. The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥10⁸-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and P(i binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the

  8. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states

    OpenAIRE

    Donnelly-Roberts, D L; Jarvis, M F

    2007-01-01

    ATP-sensitive P2X7 receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X7 receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin-1β and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X7 receptor activation indicate a role in inflammatory proces...

  9. Patterns and expenditures of multi-morbidity in an insured working population in the United States: insights for a sustainable health care system and building healthier lives.

    Science.gov (United States)

    Greene, Robert; Dasso, Edwin; Ho, Sam; Frank, Jerry; Scandrett, Graeme; Genaidy, Ash

    2013-12-01

    The U.S. health care system is currently heading toward unsustainable health care expenditures and increased dissatisfaction with health outcomes. The objective of this population-based study is to uncover practical insights regarding patients with 1 or more chronic illnesses. A cross-sectional investigation was designed to gather data from health records drawn from diverse US geographic markets. A database of 9.74 million fully-insured, working individuals was used, together with members in the same households. Among nearly 3.43 million patients with claims, 2.22 million had chronic conditions. About 24.3% had 1 chronic condition and 40.4% had multi-morbidity. Health care expenditures for chronic conditions accounted for 92% of all costs (52% for chronic costs and 40% for nonchronic costs). Psychiatry, orthopedics-rheumatology, endocrinology, and cardiology areas accounted for two thirds of these chronic condition costs; nonchronic condition costs were dominated by otolaryngology, gastroenterology, dermatology, orthopedics-rheumatology conditions, and preventive services. About 50.1% of all households had 2 or more members with chronic conditions. In summary, multi-morbidity is prevalent not only among those older than age 65 years but also in younger and working individuals, and commonly occurs among several members of a household. The authors suggest that the disease-focused model of medicine should change to a more holistic illness-wellness model, emphasizing not only the physical but also the mental and social elements that can influence individual health. In that way the chronic care model could be broadened in context and content to improve the health of patients and households.

  10. Excited state potential energy surfaces and their interactions in Fe(IV)=O active sites.

    Science.gov (United States)

    Srnec, Martin; Wong, Shaun D; Solomon, Edward I

    2014-12-21

    The non-heme ferryl active sites are of significant interest for their application in biomedical and green catalysis. These sites have been shown to have an S = 1 or S = 2 ground spin state; the latter is functional in biology. Low-temperature magnetic circular dichroism (LT MCD) spectroscopy probes the nature of the excited states in these species including ligand-field (LF) states that are otherwise difficult to study by other spectroscopies. In particular, the temperature dependences of MCD features enable their unambiguous assignment and thus determination of the low-lying excited states in two prototypical S = 1 and S = 2 NHFe(IV)[double bond, length as m-dash]O complexes. Furthermore, some MCD bands exhibit vibronic structures that allow mapping of excited-state interactions and their effects on the potential energy surfaces (PESs). For the S = 2 species, there is also an unusual spectral feature in both near-infrared absorption and MCD spectra - Fano antiresonance (dip in Abs) and Fano resonance (sharp peak in MCD) that indicates the weak spin-orbit coupling of an S = 1 state with the S = 2 LF state. These experimental data are correlated with quantum-chemical calculations that are further extended to analyze the low-lying electronic states and the evolution of their multiconfigurational characters along the Fe-O PESs. These investigations show that the lowest-energy states develop oxyl Fe(III) character at distances that are relevant to the transition state (TS) for H-atom abstraction and define the frontier molecular orbitals that participate in the reactivity of S = 1 vs. S = 2 non-heme Fe(IV)[double bond, length as m-dash]O active sites. The S = 1 species has only one available channel that requires the C-H bond of a substrate to approach perpendicular to the Fe-oxo bond (the π channel). In contrast, there are three channels (one σ and two π) available for the S = 2 non-heme Fe(IV)[double bond, length as m-dash]O system allowing C-H substrate approach

  11. INSIGHT ON THE THEROPOD FAUNA FROM THE UBERABA FORMATION (BAURU GROUP, MINAS GERAIS STATE: NEW MEGARAPTORAN SPECIMEN FROM THE LATE CRETACEOUS OF BRAZIL

    Directory of Open Access Journals (Sweden)

    AGUSTÍN G. MARTINELLI

    2013-07-01

    Full Text Available The first bony theropod record from the Campanian Uberaba Formation (Bauru Group is described. It consists of an isolated caudal centrum (CPPLIP 1324 found in the city of Uberaba, Minas Gerais State, Brazil. The amphicoelous centrum possesses a length to height ratio of 1.74, deep elliptical lateral pneumatic foramen representing 26% of centrum length with three main sub-circular air chambers, andcamellate internal structure.This combination of features is shared with Aerosteon, Megaraptor, and Orkoraptor from the Late Cretaceous of Argentinaand with the Megaraptora indet. fromthe São José do Rio Preto Formation (Bauru Group, São Paulo State,allowing us to refer it to the Megaraptora clade (Tetanurae, Neovenatoridae. As such, the new specimen represents the second megaraptoran from the Late Cretaceous of Brazil and provides new information on tail anatomy on this bizarre group. 

  12. Ferromagnetism and topological surface states of manganese doped Bi{sub 2}Te{sub 3}: Insights from density-functional calculations

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuanchang [National Center for Nanoscience and Technology, Beijing 100190 (China); Zou, Xiaolong [Department of Materials Science and Nanoengineering, Rice University, Houston, Texas 77005 (United States); Li, Jia, E-mail: lijia@phys.tsinghua.edu.cn [Key Laboratory of Thermal Management Engineering and Materials, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Zhou, Gang [Department of Physics, Tsinghua University, Beijing 100084 (China)

    2014-03-28

    Based on first-principles calculations, the electronic, magnetic, and topological characters of manganese (Mn) doped topological insulator Bi{sub 2}Te{sub 3} were investigated. The Mn substitutionally doped Bi{sub 2}Te{sub 3}, where Mn atoms tend to be uniformly distributed, was shown to be p-type ferromagnetic, arising from hole-mediated Ruderman-Kittel-Kasuya-Yosida interaction. Mn doping leads to an intrinsic band splitting at Γ point, which is substantially different from that of nonmagnetic dopant. The topological surface state of Bi{sub 2}Te{sub 3} is indeed gapped by Mn doping; however, the bulk conductance limits the appearance of an insulating state. Moreover, the n-type doping behavior of Bi{sub 2}Te{sub 3} is derived from Mn entering into the van der Waals gap of Bi{sub 2}Te{sub 3}.

  13. Exercise and limitations in physical activity levels among new dialysis patients in the United States: an epidemiologic study.

    LENUS (Irish Health Repository)

    Stack, Austin G

    2008-12-01

    Epidemiologic studies of physical activity among patients with end-stage renal disease (ESRD) are lacking. The aim of this study was to describe the patterns of physical activity among new dialysis patients in the United States.

  14. Disorganization of Equilibrium Directional Interactions in the Brain Motor Network of Parkinson's disease: New Insight of Resting State Analysis Using Granger Causality and Graphical Approach

    OpenAIRE

    Ghasemi, Mahdieh; Mahloojifar, Ali

    2013-01-01

    Parkinson's disease (PD) is a progressive neurological disorder characterized by tremor, rigidity, and slowness of movements. Particular changes related to various pathological attacks in PD could result in causal interactions of the brain network from resting state functional magnetic resonance imaging (rs-fMRI) data. In this paper, we aimed to disclose the network structure of the directed influences over the brain using multivariate Granger causality analysis and graph theory in patients w...

  15. Transition of arrestin into the active receptor-binding state requires an extended interdomain hinge.

    Science.gov (United States)

    Vishnivetskiy, Sergey A; Hirsch, Joel A; Velez, Maria-Gabriela; Gurevich, Yulia V; Gurevich, Vsevolod V

    2002-11-15

    Arrestins selectively bind to the phosphorylated activated form of G protein-coupled receptors, thereby blocking further G protein activation. Structurally, arrestins consist of two domains topologically connected by a 12-residue long loop, which we term the "hinge" region. Both domains contain receptor-binding elements. The relative size and shape of arrestin and rhodopsin suggest that dramatic changes in arrestin conformation are required to bring all of its receptor-binding elements in contact with the cytoplasmic surface of the receptor. Here we use the visual arrestin/rhodopsin system to test the hypothesis that the transition of arrestin into its active receptor-binding state involves a movement of the two domains relative to each other that might be limited by the length of the hinge. We have introduced three insertions and 24 deletions in the hinge region and measured the binding of all of these mutants to light-activated phosphorylated (P-Rh*), dark phosphorylated (P-Rh), dark unphosphorylated (Rh), and light-activated unphosphorylated rhodopsin (Rh*). The addition of 1-3 extra residues to the hinge has no effect on arrestin function. In contrast, sequential elimination of 1-8 residues results in a progressive decrease in P-Rh* binding without changing arrestin selectivity for P-Rh*. These results suggest that there is a minimum length of the hinge region necessary for high affinity binding, consistent with the idea that the two domains move relative to each other in the process of arrestin transition into its active receptor-binding state. The same length of the hinge is also necessary for the binding of "constitutively active" arrestin mutants to P-Rh*, dark P-Rh, and Rh*, suggesting that the active (receptor-bound) arrestin conformation is essentially the same in both wild type and mutant forms.

  16. Modeling for Insights

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Gretchen Matthern

    2007-04-01

    System Dynamics is a computer-aided approach to evaluating the interrelationships of different components and activities within complex systems. Recently, System Dynamics models have been developed in areas such as policy design, biological and medical modeling, energy and the environmental analysis, and in various other areas in the natural and social sciences. The real power of System Dynamic modeling is gaining insights into total system behavior as time, and system parameters are adjusted and the effects are visualized in real time. System Dynamic models allow decision makers and stakeholders to explore long-term behavior and performance of complex systems, especially in the context of dynamic processes and changing scenarios without having to wait decades to obtain field data or risk failure if a poor management or design approach is used. The Idaho National Laboratory recently has been developing a System Dynamic model of the US Nuclear Fuel Cycle. The model is intended to be used to identify and understand interactions throughout the entire nuclear fuel cycle and suggest sustainable development strategies. This paper describes the basic framework of the current model and presents examples of useful insights gained from the model thus far with respect to sustainable development of nuclear power.

  17. Resolving the 3D spatial orientation of helix I in the closed state of the colicin E1 channel domain by FRET. Insights into the integration mechanism.

    Science.gov (United States)

    Lugo, Miguel R; Ho, Derek; Merrill, A Rod

    2016-10-15

    Current evidence suggests that the closed-state membrane model for the channel-forming domain of colicin E1 involves eight amphipathic α-helices (helices I-VII and X) that adopt a two-dimensional arrangement on the membrane surface. Two central hydrophobic α-helices in colicin E1 (VIII and IX) adopt a transmembrane location-the umbrella model. Helices I and II have been shown to participate in the channel by forming a transmembrane segment (TM1) in the voltage-induced open channel state. Consequently, it is paramount to determine the relative location and orientation of helix I in the two-dimensional arrangement of the membrane. A new, low-resolution, three-dimensional model of the closed state of the colicin E1 channel was constructed based on FRET measurements between three naturally occurring Trp residues and three sites in helix I, in addition to previously reported FRET distances for the channel domain. Furthermore, a new mechanism for the channel integration process involving the transition of the soluble to membrane-bound form is presented based on a plethora of kinetic data for this process.

  18. Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation.

    Science.gov (United States)

    Sawada, N; Nagahara, N; Arisaka, F; Mitsuoka, K; Minami, M

    2011-06-01

    The oligomeric state of human porphobilinogen synthase (PBGS) [EC.4.2.1.24] is homooctamer, which consists of conformationally heterogenous subunits in the tertiary structure under air-saturated conditions. When PBGS is activated by reducing agent with zinc ion, a reservoir zinc ion coordinated by Cys(223) is transferred in the active center to be coordinated by Cys(122), Cys(124), and Cys(132) (Sawada et al. in J Biol Inorg Chem 10:199-207, 2005). The latter zinc ion serves as an electrophilic catalysis. In this study, we investigated a conformational change associated with the PBGS activation by reducing agent and zinc ion using analytical ultracentrifugation, negative staining electron microscopy, native PAGE, and enzyme activity staining. The results are in good agreement with our notion that the main component of PBGS is octamer with a few percent of hexamer and that the octamer changes spatial subunit arrangement upon reduction and further addition of zinc ion, accompanying decrease in f/f (0). It is concluded that redox-regulated PBGS activation via cleavage of disulfide bonds among Cys(122), Cys(124), and Cys(132) and coordination with zinc ion is closely linked to change in the oligomeric state.

  19. Prevalence of fruit and vegetable consumption and physical activity by race/ethnicity--United States, 2005.

    Science.gov (United States)

    2007-04-06

    Diets high in fruits and vegetables and participation in regular physical activity are associated with a lower risk for several chronic diseases and conditions. The National Cholesterol Education Program and the American Cancer Society both emphasize lifestyle modifications that include diet and physical activity to reduce disease risk. These are also two of the strategies implemented by states participating in CDC's Nutrition and Physical Activity Program to Prevent Obesity and Other Chronic Diseases. To examine the combined prevalence of 1) consumption of fruits and vegetables five or more times per day and 2) regular physical activity among U.S. adults by race/ethnicity, CDC analyzed self-reported data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS). This report describes the results of that analysis, which indicated that the combined prevalence of these two behavioral strategies was higher among men of multiple/other races (16.5%) compared with non-Hispanic white men (12.6%). In addition, only 12.6% of non-Hispanic black women and 14.8% of Hispanic women, compared with 17.4% of non-Hispanic white women, engaged in these two behavioral strategies. These results underscore the need to promote diets high in fruits and vegetables and regular physical activity among all populations in the United States and among racial and ethnic minority communities in particular.

  20. Control and dynamic competition of bright and dark lasing states in active nanoplasmonic metamaterials

    CERN Document Server

    Wuestner, Sebastian; Pusch, Andreas; Renn, Fabian; Tsakmakidis, Kosmas L; Hess, Ortwin

    2011-01-01

    Active nanoplasmonic metamaterials support bright and dark modes that compete for gain. Using a Maxwell-Bloch approach incorporating Langevin noise we study the lasing dynamics in an active nano-fishnet structure. We report that lasing of the bright negative-index mode is possible if the higher-Q dark mode is discriminated by gain, spatially or spectrally. The nonlinear competition during the transient phase is followed by steady-state emission where bright and dark modes can coexist. We analyze the influence of pump intensity and polarization and explore methods for mode control.

  1. Active Particles with Soft and Curved Walls: Equation of State, Ratchets, and Instabilities.

    Science.gov (United States)

    Nikola, Nikolai; Solon, Alexandre P; Kafri, Yariv; Kardar, Mehran; Tailleur, Julien; Voituriez, Raphaël

    2016-08-26

    We study, from first principles, the pressure exerted by an active fluid of spherical particles on general boundaries in two dimensions. We show that, despite the nonuniform pressure along curved walls, an equation of state is recovered upon a proper spatial averaging. This holds even in the presence of pairwise interactions between particles or when asymmetric walls induce ratchet currents, which are accompanied by spontaneous shear stresses on the walls. For flexible obstacles, the pressure inhomogeneities lead to a modulational instability as well as to the spontaneous motion of short semiflexible filaments. Finally, we relate the force exerted on objects immersed in active baths to the particle flux they generate around them.

  2. Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Noriko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Kimura, Tohru, E-mail: tkimura@patho.med.osaka-u.ac.jp [Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Watanabe-Kushima, Shoko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Shinohara, Takashi [Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Nakano, Toru, E-mail: tnakano@patho.med.osaka-u.ac.jp [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2010-02-12

    Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

  3. Chinese Speech Recognition Model Based on Activation of the State Feedback Neural Network

    Institute of Scientific and Technical Information of China (English)

    李先志; 孙义和

    2001-01-01

    This paper proposes a simplified novel speech recognition model, the state feedback neuralnetwork activation model (SFNNAM), which is developed based on the characteristics of Chinese speechstructure. The model assumes that the current state of speech is only a correction of the last previous state.According to the "C-V"(Consonant-Vowel) structure of the Chinese language, a speech segmentation methodis also implemented in the SFNNAM model. This model has a definite physical meaning grounded on thestructure of the Chinese language and is easily implemented in very large scale integrated circuit (VLSI). In thespeech recognition experiment, less calculations were need than in the hidden Markov models (HMM) basedalgorithm. The recognition rate for Chinese numbers was 93.5% for the first candidate and 99.5% for the firsttwo candidates.``

  4. Solid State Dye Solar Cells with Metallic Regenerators towards devices with enhanced active area

    Energy Technology Data Exchange (ETDEWEB)

    Lenzmann, F.O.; Olson, C.; Pichon, P.Y.; Heurtault, B.; Goris, M.J.A.A.; Budel, T. [ECN Solar Energy, Westerduinweg 3, NL-1755 LE Petten (Netherlands)

    2007-08-15

    In an alternative approach to solid state dye solar cells a molecular dye is situated at the interface between a TiO2 film and a metallic (Au) film. In a proof of principle with flat model devices, we have shown earlier that the Au layer efficiently regenerates the charge-neutral state of the dye upon electron injection into the TiO2 conduction band under illumination. For practically more relevant devices an increased active area is required for enhanced current output. A specially adapted TiO2 morphology with nanotubular morphology can minimize reflection losses from the metallic regenerator. In this paper the preparation of such films on transparent SnO2:F-coated glass substrates by electrochemical anodization of titanium layers is described. The focus is on preparative parameters with direct influence on film properties relevant to the application in solid-state dye solar cells (transparency and mechanical integrity of the layers)

  5. Composition Related Electrical Active Defect States of InGaAs and GaAsN

    Directory of Open Access Journals (Sweden)

    Arpad Kosa

    2017-01-01

    Full Text Available This paper discusses results of electrically active defect states - deep energy level analysis in InGaAs and GaAsN undoped semiconductor structures grown for solar cell applications. Main attention is focused on composition and growth condition dependent impurities and the investigation of their possible origins. For this purpose a widely utilized spectroscopy method, Deep Level Transient Fourier Spectroscopy, was utilized. The most significant responses of each sample labelled as InG2, InG3 and NG1, NG2 were discussed in detail and confirmed by simulations and literature data. The presence of a possible dual conduction type and dual state defect complex, dependent on the In/N composition, is reported. Beneficial characteristics of specific indium and nitrogen concentrations capable of eliminating or reducing certain point defects and dislocations are stated.

  6. Slow State Transitions of Sustained Neural Oscillations by Activity-Dependent Modulation of Intrinsic Excitability

    Science.gov (United States)

    Fröhlich, Flavio; Bazhenov, Maxim; Timofeev, Igor; Steriade, Mircea; Sejnowski, Terrence J.

    2010-01-01

    Little is known about the dynamics and mechanisms of transitions between tonic firing and bursting in cortical networks. Here, we use a computational model of a neocortical circuit with extracellular potassium dynamics to show that activity-dependent modulation of intrinsic excitability can lead to sustained oscillations with slow transitions between two distinct firing modes: fast run (tonic spiking or fast bursts with few spikes) and slow bursting. These transitions are caused by a bistability with hysteresis in a pyramidal cell model. Balanced excitation and inhibition stabilizes a network of pyramidal cells and inhibitory interneurons in the bistable region and causes sustained periodic alternations between distinct oscillatory states. During spike-wave seizures, neocortical paroxysmal activity exhibits qualitatively similar slow transitions between fast run and bursting. We therefore predict that extracellular potassium dynamics can cause alternating episodes of fast and slow oscillatory states in both normal and epileptic neocortical networks. PMID:16763023

  7. [Innovative activity of dental faculty staff of Omsk State Medical University: results, problems and prospects].

    Science.gov (United States)

    Novikov, A I; Gudinova, Zh V

    2015-01-01

    The article summarizes innovative activity in Omsk State Medical University (OSMU) and contains the review of innovative developments of staff of dental faculty of OSMU (a line of gels for caries prevetion, the DENTEST diagnostic unit, technology of tooth shape modular restoration, personified therapy.of patients with periodontal disease, caries diagnosis and periodontontal disease prognosis software, a set of the training materials on esthetic modeling of teeth, personification of clinical approaches in oral bioaesthetic rehabilitation, etc.). The analysis of the factors stimulating and complicating innovative detail in medical school, problems of introduction of medical innovations, lack of system of an assessment of medical technologies in Russia, regulations of the organization of innovative activity in medical schools is carried out, the prospects of their solution connected with decision-making at the state level are formulated.

  8. Periodicity Signatures of Lightcurves of Active Comets in Non-Principal-Axis Rotational States

    Science.gov (United States)

    Samarasinha, Nalin H.; Mueller, Beatrice E. A.; Barrera, Jose G.

    2016-10-01

    There are two comets (1P/Halley, 103P/Hartley 2) that are unambiguously in non-principal-axis (NPA) rotational states in addition to a few more comets that are candidates for NPA rotation. Considering this fact, and the ambiguities associated with how to accurately interpret the periodicity signatures seen in lightcurves of active comets, we have started an investigation to identify and characterize the periodicity signatures present in simulated lightcurves of active comets. We carried out aperture photometry of simulated cometary comae to generate model lightcurves and analyzed them with Fourier techniques to identify their periodicity signatures. These signatures were then compared with the input component periods of the respective NPA rotational states facilitating the identification of how these periodicity signatures are related to different component periods of the NPA rotation. Ultimately, we also expect this study to shed light on why only a small fraction of periodic comets is in NPA rotational states, whereas theory indicates a large fraction of them should be in NPA states (e.g., Jewitt 1999, EMP, 79, 35). We explore the parameter space with respect to different rotational states, different orientations for the total rotational angular momentum vector, and different locations on the nucleus for the source region(s). As for special cases, we also investigate potential NPA rotational states representative of comet 103P/Hartley2, the cometary target of the EPOXI mission. The initial results from our investigation will be presented at the meeting. The NASA DDAP Program supports this work through grant NNX15AL66G.

  9. The State of Anxiety Felt by Elementary School Pupils during Foreign Language Activities

    OpenAIRE

    松宮, 奈賀子

    2010-01-01

    This paper aims to investigate the state of anxiety felt by elementary school pupils while they are in foreign language activities classes. "Foreign language anxiety" is considered to have negative effects to the learners' learning and thus should be taken away. However, the foreign language anxiety has been believed to relate basically to the adult learners and few studies have been conducted which deals young learners' anxiety on foreign language learning. In this paper, about 1,500 element...

  10. Alkali activated materials state-of-the-art report, RILEM TC 224-AAM

    CERN Document Server

    Deventer, Jannie

    2014-01-01

    This is a State of the Art Report resulting from the work of RILEM Technical Committee 224-AAM in the period 2007-2013. The Report summarises research to date in the area of alkali-activated binders and concretes, with a particular focus on the following areas: binder design and characterisation, durability testing, commercialisation, standardisation, and providing a historical context for this rapidly-growing research field.

  11. Ultrafast dynamics and anionic active states of the flavin cofactor in cryptochrome and photolyase.

    Science.gov (United States)

    Kao, Ya-Ting; Tan, Chuang; Song, Sang-Hun; Oztürk, Nuri; Li, Jiang; Wang, Lijuan; Sancar, Aziz; Zhong, Dongping

    2008-06-18

    We report here our systematic studies of the dynamics of four redox states of the flavin cofactor in both photolyases and insect type 1 cryptochromes. With femtosecond resolution, we observed ultrafast photoreduction of oxidized state flavin adenine dinucleotide (FAD) in subpicosecond and of neutral radical semiquinone (FADH(*)) in tens of picoseconds through intraprotein electron transfer mainly with a neighboring conserved tryptophan triad. Such ultrafast dynamics make these forms of flavin unlikely to be the functional states of the photolyase/cryptochrome family. In contrast, we find that upon excitation the anionic semiquinone (FAD(*-)) and hydroquinone (FADH(-)) have longer lifetimes that are compatible with high-efficiency intermolecular electron transfer reactions. In photolyases, the excited active state (FADH(-)*) has a long (nanosecond) lifetime optimal for DNA-repair function. In insect type 1 cryptochromes known to be blue-light photoreceptors the excited active form (FAD(*-)*) has complex deactivation dynamics on the time scale from a few to hundreds of picoseconds, which is believed to occur through conical intersection(s) with a flexible bending motion to modulate the functional channel. These unique properties of anionic flavins suggest a universal mechanism of electron transfer for the initial functional steps of the photolyase/cryptochrome blue-light photoreceptor family.

  12. Oxygen fugacity determined from iron oxidation state in natural (Mg,Fe)O ferropericlase: new insights for lower mantle diamond formation

    Science.gov (United States)

    Longo, M.; McCammon, C.; Bulanova, G.; Kaminsky, F. V.; Tappert, R.

    2009-12-01

    The most common mineral found in diamonds originating in the lower mantle is (Mg,Fe)O ferropericlase (more than 50 percent of occurrences). Since it is well known that the Fe3+ concentration in (Mg,Fe)O is sensitive to oxygen fugacity, even at high pressures, the determination of Fe3+ over Fe total in such inclusions provides a direct method for investigating lower mantle redox conditions during diamond formation. Therefore, the goal of this study is to measure Fe3+ using a new method, namely the flank method (EMPA) in (Mg,Fe)O lower mantle diamond inclusions from a wide range of sites worldwide in order to explore the variation of oxygen fugacity with chemical, physical and geographic parameters. Eighteen (Mg,Fe)O ferropericlase inclusions from ultra deep diamonds selected worldwide (four from Juina area, Brazil, two from Machado River, Brazil, and twelve from Ororoo, Australia) were analyzed by the flank method. Inclusions were all less than 50 microns in size. Our results follow the theoretical trend described by the synthetic samples, confirming high phase homogeneity for most of the samples. Flank method measurements show a large range of redox conditions for (Mg,Fe)O inclusions, with a Fe3+ over Fe total ratio varying between 1 and 15 percent, similar to results for a suite of much larger diameter inclusions that were studied using Mössbauer spectroscopy. Inclusions recovered from the same host diamond show a strong redox gradient, which leads to the conclusion of varying oxygen fugacity conditions involved in the formation of the inclusions. These observations combined with the geographical correlation observed among all inclusions measured in the present work and from previous studies in literature leads to the suggestion of other mechanisms than subducted slabs being involved in diamond formation. In order to provide insights on the mechanisms controlling the redox conditions at lower mantle depths and how a heterogeneous oxygen fugacity may affect the

  13. THE DEVELOPMENT OF STATE AND PUBLIC MANAGEMENT OF EDUCATION THROUGH PROFESSIONAL ASSESSMENT OF INNOVATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Valery N. Volkov

    2015-01-01

    Full Text Available The aim of this investigation is to determine the influences of professional and public assessment of innovation in the general educational system for development of state and public management of education and the modeling of the implementation of such assessment.Methods. The methods involve analysis of strategic projects and innovative infrastructure of the Russian educational system; generalisation of the experience of the educational systems of the regions in the field of state and public management of education and management of innovation; modelling of professional and public expertise innovation activity.Results and scientific novelty. The impact of strategic projects of development of the Russian education on the development of state and public management of education is presented. The model of professional-public assessment of innovation in the regional general educational system is proposed; the basic procedures, subjects and standards are noted. The process approach was used while designing the model; the algorithm of professional-public assessment of innovation activity is described.Practical significance. The results of practical using of the model for professional-public assessment of innovation activity in the educational system ofSt. Petersburgare presented.

  14. THE DEVELOPMENT OF STATE AND PUBLIC MANAGEMENT OF EDUCATION THROUGH PROFESSIONAL ASSESSMENT OF INNOVATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Valery N. Volkov

    2015-07-01

    Full Text Available The aim of this investigation is to determine the influences of professional and public assessment of innovation in the general educational system for development of state and public management of education and the modeling of the implementation of such assessment.Methods. The methods involve analysis of strategic projects and innovative infrastructure of the Russian educational system; generalisation of the experience of the educational systems of the regions in the field of state and public management of education and management of innovation; modelling of professional and public expertise innovation activity.Results and scientific novelty. The impact of strategic projects of development of the Russian education on the development of state and public management of education is presented. The model of professional-public assessment of innovation in the regional general educational system is proposed; the basic procedures, subjects and standards are noted. The process approach was used while designing the model; the algorithm of professional-public assessment of innovation activity is described.Practical significance. The results of practical using of the model for professional-public assessment of innovation activity in the educational system ofSt. Petersburgare presented.

  15. Kohler's Insight Revisited.

    Science.gov (United States)

    Windholtz, George

    1985-01-01

    Psychology textbooks frequently present Wolfgang Kohler's two-stick experiment with chimpanzees as having demonstrated insight in learning. Studies that replicated Kohler's work support his findings but not his interpretation in terms of insightful solution. The uncritical inclusion of Kohler's insight interpretation in texts is not warranted in…

  16. Insights following change in drug policy: A descriptive study for antimalarial prescription practices in children of public sector health facilities in Jharkhand state of India

    Directory of Open Access Journals (Sweden)

    Neelima Mishra

    2013-12-01

    Full Text Available Background & objectives: Widespread resistance to chloroquine was the mainstay to implement artemisininbased combination therapy (ACT in the year 2007 in few malaria endemic states in India including Jharkhand as the first line of treatment for uncomplicated Plasmodium falciparum malaria. This study was conducted in Jharkhand state of the country just after the implementation of ACT to assess the prevailing antimalarial drug prescribing practices, availability of antimalarial drugs and the acceptability of the new policy by the health professionals for the treatment of uncomplicated P. falciparum malaria patients particularly in children ≤15 yr of age. Methods: This is a cross-sectional study in children aged ≤15 yr with malaria or to whom antimalarial drug was prescribed. Main outcome measure was prescription of recommended ACT in children aged ≤15 yr with malaria in the selected areas of Jharkhand. Results: In the year 2008, artemisinin-based combination therapy (ACT was implemented in 12 districts of the studied state; however, the availability of ACT was confirmed only in five districts. Antimalarial prescription was prevalent amongst the undiagnosed (8.4%, malaria negative (64.3% and unknown blood test result (1.2% suggesting the prevalence of irrational treatment practices. ACT prescription was very low with only 3.2% of confirmed falciparum malaria patients receiving it while others received either non-artesunate (NA treatment (88.1% including chloroquine (CQ alone, CQ + Primaquine (PQ/other drugs, sulphadoxine-pyrimethamine (SP alone, SP + other drugs or artemisinin monotherapy (AM treatment (6.3%. Still others were given nonantimalarial treatment (NM in both malaria positive (0.3% and malaria negative (2.1% cases. Interpretation & conclusion: Despite the change in drug policy in the studied state the availability and implementation of ACT was a major concern. Nevertheless, the non-availability of blister packs for children aged

  17. Exploring the Linkage between Activity-Friendly Zoning, Inactivity, and Cancer Incidence in the United States.

    Science.gov (United States)

    Nicholson, Lisa M; Leider, Julien; Chriqui, Jamie F

    2017-03-07

    Background: Physical activity (PA) protects against cancer and enhances cancer survivorship. Given high inactivity rates nationwide, population-level physical activity facilitators are needed. Several authoritative bodies have recognized that zoning and planning helps create activity-friendly environments. This study examined the association between activity-friendly zoning, inactivity, and cancer in 478 of the most populous U.S. counties.Methods: County geocodes linked county-level data: cancer incidence and smoking (State Cancer Profiles), inactivity (Behavioral Risk Factor Surveillance System), 11 zoning measures (compiled by the study team), and covariates (from the American Community Survey and NAVTEQ). For each zoning measure, single mediation regression models and Sobel tests examined whether activity-friendly zoning was associated with reduced cancer incidence, and whether inactivity mediated those associations. All models were clustered on state with robust SEs and significance at the P Zoning for crosswalks, bike-pedestrian connectivity, and bike-pedestrian trails/paths were associated with reduced cancer incidence (β between -0.71 and -1.27, P zoning. Except for crosswalks, each association was mediated by inactivity. However, county smoking attenuated these results, with only crosswalks remaining significant. Results were similar for males (with zoning for bike-pedestrian connectivity, street connectivity, and bike-pedestrian trails/paths), but not females, alone.Conclusions: Zoning can help to create activity-friendly environments that support decreased inactivity, and possibly reduced cancer incidence.Impact: Given low physical activity levels nationwide, cross-sectoral collaborations with urban planning can inform cancer prevention and public health efforts to decrease inactivity and cancer. Cancer Epidemiol Biomarkers Prev; 1-9. ©2017 AACR.See all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population

  18. New insight into the dynamic properties and the active site architecture of H-Ras p21 revealed by X-ray crystallography at very high resolution

    Directory of Open Access Journals (Sweden)

    Klink Björn U

    2010-10-01

    Full Text Available Abstract Background In kinetic crystallography, the usually static method of X-ray diffraction is expanded to allow time-resolved analysis of conformational rearrangements in protein structures. To achieve this, reactions have to be triggered within the protein crystals of interest, and optical spectroscopy can be used to monitor the reaction state. For this approach, a modified form of H-Ras p21 was designed which allows reaction initiation and fluorescence readout of the initiated GTPase reaction within the crystalline state. Rearrangements within the crystallized protein due to the progressing reaction and associated heterogeneity in the protein conformations have to be considered in the subsequent refinement processes. Results X-ray diffraction experiments on H-Ras p21 in different states along the reaction pathway provide detailed information about the kinetics and mechanism of the GTPase reaction. In addition, a very high data quality of up to 1.0 Å resolution allowed distinguishing two discrete subconformations of H-Ras p21, expanding the knowledge about the intrinsic flexibility of Ras-like proteins, which is important for their function. In a complex of H-Ras•GppNHp (guanosine-5'-(β,γ-imido-triphosphate, a second Mg2+ ion was found to be coordinated to the γ-phosphate group of GppNHp, which positions the hydrolytically active water molecule very close to the attacked γ-phosphorous atom. Conclusion For the structural analysis of very high-resolution data we have used a new 'two-chain-isotropic-refinement' strategy. This refinement provides an alternative and easy to interpret strategy to reflect the conformational variability within crystal structures of biological macromolecules. The presented fluorescent form of H-Ras p21 will be advantageous for fluorescence studies on H-Ras p21 in which the use of fluorescent nucleotides is not feasible.

  19. Efficiency of state financial support of export activity of small and medium businesses

    Directory of Open Access Journals (Sweden)

    Timur R. Urumov

    2017-03-01

    Full Text Available Objective to assess the effectiveness and role of state financial support of export activities of small and medium enterprises. Methods regression analysis abstractlogical method method of comparison. Results the need is identified to evaluate the impact of state programs of export support on the results of export operations as a mechanism for assessing the efficiency of public spending in this area. The institutions are analyzed of state support of export of small and medium businesses production in the USA and India. It is revealed that in the US the main tool of support are export credits and guarantees while in India the emphasis is on the promotion of products to the world markets. To assess the effectiveness of public expenditure on export support the data were collected and systematized on the total volume of export and the costs of its support in the United States and India. The project revealed the presence of a time lag between these indices. When building a regression model the method of least squares was applied on the basis of which three hypotheses were investigated namely those taking into account and not taking into account the presence of the time lag between variables. As a result of constructing the model it was found that in the U.S. the increase in budget spending on export support to 1mln leads to an increase in export volume to 2mln. In India the corresponding figure was 10mln. The analysis of the Russian practice of the state support of export of the small and medium businesses production showed a lack of systematic approach and poor development of the small business sector compared to the studied countries. Scientific novelty the positive relationship was revealed between the costs of exports support and export sales in the United States and India. The necessity was grounded of state the financial support of export activities of small and medium enterprises in Russia as well as product promotion through sectoral

  20. Disorganization of Equilibrium Directional Interactions in the Brain Motor Network of Parkinson's disease: New Insight of Resting State Analysis Using Granger Causality and Graphical Approach.

    Science.gov (United States)

    Ghasemi, Mahdieh; Mahloojifar, Ali

    2013-04-01

    Parkinson's disease (PD) is a progressive neurological disorder characterized by tremor, rigidity, and slowness of movements. Particular changes related to various pathological attacks in PD could result in causal interactions of the brain network from resting state functional magnetic resonance imaging (rs-fMRI) data. In this paper, we aimed to disclose the network structure of the directed influences over the brain using multivariate Granger causality analysis and graph theory in patients with PD as compared with control group. rs-fMRI at rest from 10 PD patients and 10 controls were analyzed. Topological properties of the networks showed that information flow in PD is smaller than that in healthy individuals. We found that there is a balanced local network in healthy control group, including positive pair-wise cross connections between caudate and cerebellum and reciprocal connections between motor cortex and caudate in the left and right hemispheres. The results showed that this local network is disrupted in PD due to disturbance of the interactions in the motor networks. These findings suggested alteration of the functional organization of the brain in the resting state that affects the information transmission from and to other brain regions related to both primary dysfunctions and higher-level cognition impairments in PD. Furthermore, we showed that regions with high degree values could be detected as betweenness centrality nodes. Our results demonstrate that properties of small-world connectivity could also recognize and quantify the characteristics of directed influence brain networks in PD.

  1. Oxygen fugacities determined from iron oxidation state in natural (Mg,Fe)O ferropericlase: new insights into lower mantle diamond formation

    Science.gov (United States)

    Longo, Micaela; McCammon, Catherine; Bulanova, Galina; Kaminsky, Felix; Tappert, Ralf

    2010-05-01

    noteworthy that a variation of oxygen fugacity was registered in multiple inclusions extracted from the same host diamonds. However, because the inclusions were removed from the host without textural control, information on the direction of any redox gradient that may have evolved, and possible correlation with diamond growth or anomalies in the variation of the redox conditions through time, were lost. These observations combined with the geographical correlation observed among all inclusions measured in the present work and from previous studies leads to the suggestion of other mechanisms than subducted slabs being involved in diamond formation. In order to provide insights on the mechanisms controlling the redox conditions at lower mantle depths and how such oxygen fugacities may affect the physical and chemical properties of the lower mantle, new measurements are planned to increase the data set on ferropericlase inclusions. Moreover, a multi disciplinary study involving cathodoluminescence studies and isotopic and optical studies is suggested for further work. References Frost et al. (2004) Nature, 428, 409-412. Longo et al., In preparation McCammon et al. (2004) Earth and Planetary Science Letters, 222, 423-434. McCammon et al. (1997) Science, 278, 434-436.

  2. Matching Element Symbols with State Abbreviations: A Fun Activity for Browsing the Periodic Table of Chemical Elements

    Science.gov (United States)

    Woelk, Klaus

    2009-01-01

    A classroom activity is presented in which students are challenged to find matches between the United States two-letter postal abbreviations for states and chemical element symbols. The activity aims to lessen negative apprehensions students might have when the periodic table of the elements with its more than 100 combinations of letters is first…

  3. Evaluating the Role of Aerosol Mixing State in Cloud Droplet Nucleation using a New Activation Parameterization

    Science.gov (United States)

    Rothenberg, D. A.; Wang, C.

    2013-12-01

    An important source contributing to uncertainty in simulations with global climate models arises from the influence of aerosols on cloud properties. These so-called aerosol indirect effects arise from a single coupling in the model, representing how aerosols activate and serve as cloud condensation nuclei and ultimately cloud droplets. While it is possible to build explicit numerical models which describe this process in detail, these class of tools are untenable for use in global climate models due to their complexity. Instead, physically- or empirically-based parameterizations of activation are used in their place to efficiently approximate cloud droplet nucleation as a function of a few meteorological and aerosol physical/chemical properties. As global climate models are outfitted with more complex, size- and mixing state-resolving aerosol models, activation parameterizations are increasingly called upon to handle aerosol populations against which their performance has not been explicitly benchmarked. Here, a simple scheme is proposed to evaluate the performance of activation parameterizations against a spectrum of mixing states, and two schemes commonly used in global models are studied using this framework. It is shown that each scheme exhibits systematic biases when a complex mixing state is present. To help resolve these issues, a new scheme is derived using Polynomial Chaos Expansion to build meta-models representing a full complexity parcel model. The meta-models are shown to accurately handle activation in both single-mode and mixture cases. In addition, a global sensitivity analysis is applied to benchmark the performance of the meta-models and the activation parameterizations against a detailed parcel model, and it is shown that the meta-models tend to more accurately attribute variability in activation dynamics to each input parameter and their interactions with others when compared to the physically-based parameterizations. A variety of experiments

  4. RELATIONSHIPS BETWEEN PHYSICAL EDUCATION STUDENTS' MOTIVATIONAL PROFILES, ENJOYMENT, STATE ANXIETY, AND SELF-REPORTED PHYSICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Sami Yli-Piipari

    2009-09-01

    Full Text Available The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000 and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213 completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1 the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2 the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education.

  5. Compression-cuticle relationship of seed ferns: Insights from liquid-solid states FTIR (Late Palaeozoic-Early Mesozoic, Canada-Spain-Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Zodrow, Erwin L. [Palaeobotanical Laboratory, Cape Breton University, Sydney, Nova Scotia (Canada); D' Angelo, Jose A. [Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales (IANIGLA), CCT-CONICET-Mendoza, Avda. Ruiz Leal s/n Parque Gral. San Martin (5500) Mendoza (Argentina); Area de Quimica, Instituto de Ciencias Basicas, Universidad Nacional de Cuyo, Centro Universitario - M5502JMA - Mendoza (Argentina); Mastalerz, Maria [Indiana Geological Survey, Indiana University, 611 North Walnut Grove, Bloomington, IN 47405-2208 (United States); Keefe, Dale [Molecular Spectroscopy Research Laboratory, Department of Chemistry, Cape Breton University, Sydney, Nova Scotia (Canada)

    2009-08-01

    Cuticles have been macerated from suitably preserved compressed fossil foliage by Schulze's process for the past 150 years, whereas the physical-biochemical relationship between the ''coalified layer'' with preserved cuticle as a unit has hardly been investigated, although they provide complementary information. This relationship is conceptualized by an analogue model of the anatomy of an extant leaf: ''vitrinite (mesophyll) + cuticle (biomacropolymer) = compression''. Alkaline solutions from Schulze's process as a proxy for the vitrinite, are studied by means of liquid-solid states Fourier transform infrared spectroscopy (FTIR). In addition, cuticle-free coalified layers and fossilized cuticles of seed ferns mainly from Canada, Spain and Argentina of Late Pennsylvanian-Late Triassic age are included in the study sample. Infrared data of cuticle and alkaline solutions differ which is primarily contingent on the mesophyll +biomacropolymer characteristics. The compression records two pathways of organic matter transformation. One is the vitrinized component that reflects the diagenetic-post-diagenetic coalification history parallel with the evolution of the associated coal seam. The other is the cuticle that reflects the sum-total of evolutionary pathway of the biomacropolymer, its monomeric, or polymeric fragmentation, though factors promoting preservation include entombing clay minerals and lower pH conditions. Caution is advised when interpreting liquid-state-based FTIR data, as some IR signals may have resulted from the interaction of Schulze's process with the cuticular biochemistry. A biochemical-study course for taphonomy is suggested, as fossilized cuticles, cuticle-free coalified layers, and compressions are responses to shared physicogeochemical factors. (author)

  6. The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State Nuclear Magnetic Resonance.

    Science.gov (United States)

    Kwon, Byungsu; Hong, Mei

    2016-09-27

    The influenza M2 protein is the target of the amantadine family of antiviral drugs, and its transmembrane (TM) domain structure and dynamics have been extensively studied. However, little is known about the structure of the highly conserved N-terminal ectodomain, which contains epitopes targeted by influenza vaccines. In this study, we synthesized an M2 construct containing the N-terminal ectodomain and the TM domain, to understand the site-specific conformation and dynamics of the ectodomain and to investigate the effect of the ectodomain on the TM structure. We incorporated (13)C- and (15)N-labeled residues into both domains and measured their chemical shifts and line widths using solid-state nuclear magnetic resonance. The data indicate that the entire ectodomain is unstructured and dynamic, but the motion is slower for residues closer to the TM domain. (13)C line shapes indicate that this ecto-TM construct undergoes fast uniaxial rotational diffusion, like the isolated TM peptide, but drug binding increases the motional rates of the TM helix while slowing the local motion of the ectodomain residues that are close to the TM domain. Moreover, (13)C and (15)N chemical shifts indicate that the ectodomain shifts the conformational equilibria of the TM residues toward the drug-bound state even in the absence of amantadine, thus providing a molecular structural basis for the lower inhibitory concentration of full-length M2 compared to that of the ectodomain-truncated M2. We propose that this conformational selection may result from electrostatic repulsion between negatively charged ectodomain residues in the tetrameric protein. Together with the recent study of the M2 cytoplasmic domain, these results show that intrinsically disordered extramembrane domains in membrane proteins can regulate the functionally relevant conformation and dynamics of the structurally ordered TM domains.

  7. Compression-cuticle relationship of seed ferns: Insights from liquid-solid states FTIR (Late Palaeozoic-Early Mesozoic, Canada-Spain-Argentina)

    Science.gov (United States)

    Zodrow, E.L.; D'Angelo, J. A.; Mastalerz, Maria; Keefe, D.

    2009-01-01

    Cuticles have been macerated from suitably preserved compressed fossil foliage by Schulze's process for the past 150 years, whereas the physical-biochemical relationship between the "coalified layer" with preserved cuticle as a unit has hardly been investigated, although they provide complementary information. This relationship is conceptualized by an analogue model of the anatomy of an extant leaf: "vitrinite (mesophyll) + cuticle (biomacropolymer) = compression". Alkaline solutions from Schulze's process as a proxy for the vitrinite, are studied by means of liquid-solid states Fourier transform infrared spectroscopy (FTIR). In addition, cuticle-free coalified layers and fossilized cuticles of seed ferns mainly from Canada, Spain and Argentina of Late Pennsylvanian-Late Triassic age are included in the study sample. Infrared data of cuticle and alkaline solutions differ which is primarily contingent on the mesophyll +biomacropolymer characteristics. The compression records two pathways of organic matter transformation. One is the vitrinized component that reflects the diagenetic-post-diagenetic coalification history parallel with the evolution of the associated coal seam. The other is the cuticle that reflects the sum-total of evolutionary pathway of the biomacropolymer, its monomeric, or polymeric fragmentation, though factors promoting preservation include entombing clay minerals and lower pH conditions. Caution is advised when interpreting liquid-state-based FTIR data, as some IR signals may have resulted from the interaction of Schulze's process with the cuticular biochemistry. A biochemical-study course for taphonomy is suggested, as fossilized cuticles, cuticle-free coalified layers, and compressions are responses to shared physicogeochemical factors. ?? 2009 Elsevier B.V. All rights reserved.

  8. Evolution of a transition state: role of Lys100 in the active site of isocitrate dehydrogenase.

    Science.gov (United States)

    Miller, Stephen P; Gonçalves, Susana; Matias, Pedro M; Dean, Antony M

    2014-05-26

    An active site lysine essential to catalysis in isocitrate dehydrogenase (IDH) is absent from related enzymes. As all family members catalyze the same oxidative β-decarboxylation at the (2R)-malate core common to their substrates, it seems odd that an amino acid essential to one is not found in all. Ordinarily, hydride transfer to a nicotinamide C4 neutralizes the positive charge at N1 directly. In IDH, the negatively charged C4-carboxylate of isocitrate stabilizes the ground state positive charge on the adjacent nicotinamide N1, opposing hydride transfer. The critical lysine is poised to stabilize-and perhaps even protonate-an oxyanion formed on the nicotinamide 3-carboxamide, thereby enabling the hydride to be transferred while the positive charge at N1 is maintained. IDH might catalyze the same overall reaction as other family members, but dehydrogenation proceeds through a distinct, though related, transition state. Partial activation of lysine mutants by K(+) and NH4 (+) represents a throwback to the primordial state of the first promiscuous substrate family member.

  9. Oligomeric state regulated trafficking of human platelet-activating factor acetylhydrolase type-II.

    Science.gov (United States)

    Monillas, Elizabeth S; Caplan, Jeffrey L; Thévenin, Anastasia F; Bahnson, Brian J

    2015-05-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response.

  10. Assessing the function of the fronto-parietal attention network: insights from resting-state fMRI and the attentional network test.

    Science.gov (United States)

    Markett, Sebastian; Reuter, Martin; Montag, Christian; Voigt, Gesine; Lachmann, Bernd; Rudorf, Sarah; Elger, Christian E; Weber, Bernd

    2014-04-01

    In the recent past, various intrinsic connectivity networks (ICN) have been identified in the resting brain. It has been hypothesized that the fronto-parietal ICN is involved in attentional processes. Evidence for this claim stems from task-related activation studies that show a joint activation of the implicated brain regions during tasks that require sustained attention. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate that functional connectivity within the fronto-parietal network at rest directly relates to attention. We applied graph theory to functional connectivity data from multiple regions of interest and tested for associations with behavioral measures of attention as provided by the attentional network test (ANT), which we acquired in a separate session outside the MRI environment. We found robust statistical associations with centrality measures of global and local connectivity of nodes within the network with the alerting and executive control subfunctions of attention. The results provide further evidence for the functional significance of ICN and the hypothesized role of the fronto-parietal attention network.

  11. Cellulase Activity in Solid State Fermentation of Palm Kernel Cake with Trichoderma sp.

    Directory of Open Access Journals (Sweden)

    Massaud, M. B. N.

    2012-01-01

    Full Text Available Aims: The effect of different types of fungal inocula to the cellulase activity measured on palm kernel cake (PKC was studied. Methodology and Results: Isolate Pro-A1 which was identified as Trichoderma sp. was selected as a potential producer of cellulase via solid state fermentation technique (SSF. Two types of PKCs were used; raw PKC (containing residual oil and defatted PKC. The PKCs were inoculated with different concentrations of conidia and varying amounts (g of solid mycelia plugs (SMP for SSF. The effect of ultrafiltered crude fungal filtrate (CFF as inocula was also being tested. The highest cellulase activity of 2.454 FPU/mL was detected with 60% (wt/wt SMP applied to the raw PKC. Conversely, 2.059 FPU/mL of cellulase activity was measured when 80% (wt/wt of SMP was applied to the defatted PKC which is 62.3% higher than the untreated defatted PKC; and more than 100% increase in enzymatic activity compared to raw PKC. The cellulase activity in the SSF inoculated with 8 x 106 conidia /mL and 12 x 106 conidia /mL were 1.704 FPU/mL for raw PKC and 1.856 FPU/mL for defatted PKC, an enhancement of about 46% from uninoculated batch. Inoculation with CFF bears corresponding maximum improvement of the cellulase activity on both PKCs of 13.58% (raw and 2.86% (defatted. Conclusion, significance and impact of study: The current study proves that Trichoderma sp. in the form of SMP can enhance the cellulase activity on PKCs effectively with more than 100% increment. Fungal conidia are also a better choice in enhancing cellulase activity of Trichoderma sp. permitted that the PKC used is devoid of oil. From this study, Trichoderma sp. holds the potential of converting lignocellulosic materials into products of commercial and industrial values such as glucose and other biofuels.

  12. Posterior cingulate cortex-related co-activation patterns: a resting state FMRI study in propofol-induced loss of consciousness.

    Directory of Open Access Journals (Sweden)

    Enrico Amico

    Full Text Available BACKGROUND: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations. METHODS: Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation. Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8, to obtain 8 different PCC co-activation patterns (CAPs for each level of consciousness. RESULTS: The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex, some others new (e.g., reduced co-activation in motor cortex and visual area. CONCLUSION: In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local

  13. The Operating Principle of a Fully Solid State Active Magnetic Regenerator

    Energy Technology Data Exchange (ETDEWEB)

    Abdelaziz, Omar [ORNL

    2016-01-01

    As an alternative refrigeration technology, magnetocaloric refrigeration has the potential to be safer, quieter, more efficient, and more environmentally friendly than the conventional vapor compression refrigeration technology. Most of the reported active magnetic regenerator (AMR) systems that operate based on the magnetocaloric effect use heat transfer fluid to exchange heat, which results in complicated mechanical subsystems and components such as rotating valves and hydraulic pumps. This paper presents an operating principle of a fully solid state AMR, in which an alternative mechanism for heat transfer between the AMR and the heat source/sink is proposed. The operating principle of the fully solid state AMR is based on moving rods/sheets (e.g. copper, brass, iron or aluminum), which are employed to replace the heat transfer fluid. Such fully solid state AMR would provide a significantly higher heat transfer rate than a conventional AMR because the conductivity of moving solid rods/plates is high and it enables the increase in the machine operating frequency hence the cooling capacity. The details of operating principle are presented and discussed here. One of the key enabling features for this technology is the contact between the moving rods/sheets and magnetocaloric material, and heat exchange mechanism at the heat source/sink. This paper provides an overview of the design for a fully solid state magnetocaloric refrigeration system along with guidelines for their optimal design.

  14. The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

    Science.gov (United States)

    Juozaityte, Vaida; Pladevall-Morera, David; Podolska, Agnieszka; Nørgaard, Steffen; Pocock, Roger

    2017-01-01

    Animal behavior is shaped through interplay among genes, the environment, and previous experience. As in mammals, satiety signals induce quiescence in Caenorhabditis elegans. Here we report that the C. elegans transcription factor ETS-5, an ortholog of mammalian FEV/Pet1, controls satiety-induced quiescence. Nutritional status has a major influence on C. elegans behavior. When foraging, food availability controls behavioral state switching between active (roaming) and sedentary (dwelling) states; however, when provided with high-quality food, C. elegans become sated and enter quiescence. We show that ETS-5 acts to promote roaming and inhibit quiescence by setting the internal “satiety quotient” through fat regulation. Acting from the ASG and BAG sensory neurons, we show that ETS-5 functions in a complex network with serotonergic and neuropeptide signaling pathways to control food-regulated behavioral state switching. Taken together, our results identify a neuronal mechanism for controlling intestinal fat stores and organismal behavioral states in C. elegans, and establish a paradigm for the elucidation of obesity-relevant mechanisms. PMID:28193866

  15. Indium-Carrier Minerals in Polymetallic Sulphide Ore Deposits: A Crystal Chemical Insight into an Indium Binding State Supported by X-ray Absorption Spectroscopy Data

    Directory of Open Access Journals (Sweden)

    Diogo Rosa

    2012-11-01

    Full Text Available Indium is a typical chalcophile element of the Earth’s crust, with a very low average content that seldom forms specific minerals, occurring mainly as dispersed in polymetallic sulphides. Indium recovery is based primarily on zinc extraction from sphalerite, the prototype of so-called tetrahedral sulphides, wherein metal ions fill half of the available tetrahedral sites within the cubic closest packing of sulphur anions, leaving interstices accessible for further in-filling. Ascertaining the tendency towards the establishment of In-In interactions through an x-ray absorption spectroscopy approach would efficiently contribute to understanding the behavior of indium in the carrier mineral. The successful results of applying such a near-edge absorption (XANES study at In L3-edge to samples collected at the Lagoa Salgada polymetallic orebody in the Iberian Pyrite Belt (IPB are described and the crystal chemistry of indium is re-evaluated, disclosing a potential clue for the metal binding state in polymetallic sulphides.

  16. Insights on the influence of surface roughness on photovoltaic properties of state of the art copper indium gallium diselenide thin films solar cells

    Science.gov (United States)

    Jehl, Z.; Bouttemy, M.; Lincot, D.; Guillemoles, J. F.; Gerard, I.; Etcheberry, A.; Voorwinden, G.; Powalla, M.; Naghavi, N.

    2012-06-01

    The influence of Cu(In,Ga)Se2 (CIGSe) surface roughness on the photovoltaic parameters of state of the art devices is reported, highlighting the importance of the roughness of the as-grown CIGSe absorbers on solar cell efficiencies. As-grown CIGSe surface is progressively smoothed using a chemical etch, and characterized by SEM, AFM, XPS, μ-Raman spectroscopy, x-ray diffraction (XRD), and reflectivity. The decrease of roughness has no marked influence on crystal structure and surface composition of the absorber. The main effect is that the total reflectivity of the CIGSe surface increases with decreasing roughness. The samples are processed into solar cells and characterized by current-voltage measurements. While the open circuit voltage (Voc) and fill factor remain constant, the short circuit current (Jsc) decreases markedly with decreasing roughness, resulting in a reduction of the solar cell efficiency from 14% down to 11%, which exceeds the expected decrease from increased reflectivity. Quantum efficiency and reflectivity measurements on complete cells are performed to analyze those effects. The influence of surface roughness on the theorical effective space charge region and diffusion length is based on a simple theoretical model. This paper discusses the comparison of CIGSe solar cells with n-i-p structures.

  17. Insights on the influence of surface roughness on photovoltaic properties of state of the art copper indium gallium diselenide thin films solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Jehl, Z.; Lincot, D.; Guillemoles, J. F.; Naghavi, N. [Institut de Recherche et Developpement sur l' Energie Photovoltaieque (IRDEP - UMR 7174 EDF/CNRS/CHIMIE-PARISTECH), 6 quai Watier, 78401 Chatou Cedex (France); Bouttemy, M.; Gerard, I.; Etcheberry, A. [ILV - UMR 8180 CNRS, Universite de Versailles St Quentin, 45 Av. des Etats Unis, 78035 Versailles CEDEX (France); Voorwinden, G. [Wuerth Elektronik Research GmbH, Industriestr. 4, 70565 Stuttgart (Germany); Powalla, M. [Zentrum fuer Sonnenenergie-und Wasserstoff-Forschung (ZSW), Industriestr. 6, 70565 Stuttgart (Germany)

    2012-06-01

    The influence of Cu(In,Ga)Se{sub 2} (CIGSe) surface roughness on the photovoltaic parameters of state of the art devices is reported, highlighting the importance of the roughness of the as-grown CIGSe absorbers on solar cell efficiencies. As-grown CIGSe surface is progressively smoothed using a chemical etch, and characterized by SEM, AFM, XPS, {mu}-Raman spectroscopy, x-ray diffraction (XRD), and reflectivity. The decrease of roughness has no marked influence on crystal structure and surface composition of the absorber. The main effect is that the total reflectivity of the CIGSe surface increases with decreasing roughness. The samples are processed into solar cells and characterized by current-voltage measurements. While the open circuit voltage (V{sub oc}) and fill factor remain constant, the short circuit current (J{sub sc}) decreases markedly with decreasing roughness, resulting in a reduction of the solar cell efficiency from 14% down to 11%, which exceeds the expected decrease from increased reflectivity. Quantum efficiency and reflectivity measurements on complete cells are performed to analyze those effects. The influence of surface roughness on the theorical effective space charge region and diffusion length is based on a simple theoretical model. This paper discusses the comparison of CIGSe solar cells with n-i-p structures.

  18. Activation of silicon quantum dots and coupling between the active centre and the defect state of the photonic crystal in a nanolaser

    Institute of Scientific and Technical Information of China (English)

    Huang Wei-Qi; Chen Hang-Qiong; Shu Qin; Liu Shi-Rong; Qin Chao-Jian

    2012-01-01

    A new nanolaser concept using silicon quantum dots (QDs) is proposed.The conduction band opened by the quantum confinement effect gives the pumping levels.Localized states in the gap due to some surface bonds on Si QDs can be formed for the activation of emission.An inversion of population can be generated between the localized states and the valence band in a QD fabricated by using a nanosecond pulse laser.Coupling between the active centres formed by localized states and the defect states of the two-dimensional (2D) photonic crystal can be used to select the model in the nanolaser.

  19. Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy.

    Science.gov (United States)

    Chen, Hua-Jun; Zhu, Xi-Qi; Yang, Ming; Liu, Bin; Zhang, Yi; Wang, Yu; Teng, Gao-Jun

    2012-01-17

    Resting-state functional magnetic resonance imaging (fMRI) has facilitated the study of spontaneous brain activity by measuring low-frequency oscillations in blood-oxygen-level-dependent signals. Analyses of regional homogeneity (ReHo), which reflects the local synchrony of neural activity, have been used to reveal the mechanisms underlying the brain dysfunction in various neuropsychiatric diseases. However, it is not known whether the ReHo is altered in cirrhotic patients with minimal hepatic encephalopathy (MHE). We recruited 18 healthy controls and 18 patients with MHE. The ReHo was calculated to assess the strength of the local signal synchrony. Compared with the healthy controls, the patients with MHE had significantly decreased ReHo in the cuneus and adjacent precuneus, and left inferior parietal lobe, whereas the regions showing increased ReHo in patients with MHE included the left parahippocampal gyrus, right cerebellar vermis, and bilateral anterior cerebellar lobes. We found a positive correlation between the mean ReHo in the cuneus and adjacent precuneus and the score on the digit-symbol test in the patient group. In conclusion, the analysis of the regional homogeneity of resting-state brain activity may provide additional information with respect to a clinical definition of MHE.

  20. Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states.

    Science.gov (United States)

    Ehmann, Nadine; van de Linde, Sebastian; Alon, Amit; Ljaschenko, Dmitrij; Keung, Xi Zhen; Holm, Thorge; Rings, Annika; DiAntonio, Aaron; Hallermann, Stefan; Ashery, Uri; Heckmann, Manfred; Sauer, Markus; Kittel, Robert J

    2014-08-18

    The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by the diffraction-limited resolution of conventional light microscopy. Here we introduce new approaches to quantify endogenous protein organization at single-molecule resolution in situ with super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of which are organized into about 15 heptameric clusters. We test for a quantitative relationship between CAZ ultrastructure and neurotransmitter release properties by engaging Drosophila mutants and electrophysiology. Our results indicate that the precise nanoscopic organization of Brp distinguishes different physiological AZ states and link functional diversification to a heretofore unrecognized neuronal gradient of the CAZ ultrastructure.

  1. Neuropeptidergic Signaling and Active Feeding State Inhibit Nociception in Caenorhabditis elegans.

    Science.gov (United States)

    Ezcurra, Marina; Walker, Denise S; Beets, Isabel; Swoboda, Peter; Schafer, William R

    2016-03-16

    Food availability and nutritional status are important cues affecting behavioral states. Here we report that, in Caenorhabditis elegans, a cascade of dopamine and neuropeptide signaling acts to inhibit nociception in food-poor environments. In the absence of food, animals show decreased sensitivity and increased adaptation to soluble repellents sensed by the polymodal ASH nociceptors. The effects of food on adaptation are affected by dopamine and neuropeptide signaling; dopamine acts via the DOP-1 receptor to decrease adaptation on food, whereas the neuropeptide receptors NPR-1 and NPR-2 act to increase adaptation off food. NPR-1 and NPR-2 function cell autonomously in the ASH neurons to increase adaptation off food, whereas the DOP-1 receptor controls neuropeptide release from interneurons that modulate ASH activity indirectly. These results indicate that feeding state modulates nociception through the interaction of monoamine and neuropeptide signaling pathways.

  2. Neuropeptidergic Signaling and Active Feeding State Inhibit Nociception in Caenorhabditis elegans

    Science.gov (United States)

    Ezcurra, Marina; Walker, Denise S.; Beets, Isabel; Swoboda, Peter

    2016-01-01

    Food availability and nutritional status are important cues affecting behavioral states. Here we report that, in Caenorhabditis elegans, a cascade of dopamine and neuropeptide signaling acts to inhibit nociception in food-poor environments. In the absence of food, animals show decreased sensitivity and increased adaptation to soluble repellents sensed by the polymodal ASH nociceptors. The effects of food on adaptation are affected by dopamine and neuropeptide signaling; dopamine acts via the DOP-1 receptor to decrease adaptation on food, whereas the neuropeptide receptors NPR-1 and NPR-2 act to increase adaptation off food. NPR-1 and NPR-2 function cell autonomously in the ASH neurons to increase adaptation off food, whereas the DOP-1 receptor controls neuropeptide release from interneurons that modulate ASH activity indirectly. These results indicate that feeding state modulates nociception through the interaction of monoamine and neuropeptide signaling pathways. PMID:26985027

  3. DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jakob Madsen Pedersen

    Full Text Available To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence, and enrichment of a nucleosome at a critical position in the promoter region, in line with a repressible/inducible mode of regulation. Single-gene studies with a range of genes belonging to this group demonstrate that topoisomerases play an important role during activation of these genes. Subsequent in-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation.

  4. Structure and tectonic setting of the SE Sardinia mafic dyke swarm. Insights for the stress state during magma emplacement in the upper crust

    Science.gov (United States)

    Martinez-Poza, Ana Isabel; Druguet, Elena

    2016-11-01

    The SE Sardinia mafic dyke swarm intruded in Permian times into the Late Variscan granitoids of the Sàrrabus massif. In order to characterize the structure of the dyke swarm and to assess the stress state and tectonic regime at the time of dyking, we have performed a multi-methodological study which encompasses paleostress analysis using the orientation distribution of dykes, estimation of crustal extension from dyke thickness/spacing ratios and true dilation direction from the matching geometry of offsets. The mean orientation of the dyke swarm is ∼N150°, with secondary main trends orientated ∼N77° and ∼N10°. The fracture network (mostly joints) exhibits multiple orientations grouped in four or more sets, being the orientation and density patterns in granitoid and dykes significantly different. Some of the pre-existing joints were exploited by the dykes, while others were reactivated as faults during and after dyke intrusion. The paleostress analysis yielded σ1 sub-vertical, indicating that an extensional tectonic regime predominated in the area during the emplacement of the dyke swarm. σ3 was sub-horizontal, sub-parallel to the mean NE-SW dilation direction. The inferred relative stress magnitudes are characterized by a σ1 much larger than the other two principal stresses. In this context, intrusion of the dyke swarm occurred under low magma pressure conditions and preferentially into a pre-existing joint nerwork during a regional extensional event. The SE Sardinian dyke swarm has been compared with other contemporary mafic dykes of the western Mediterranean region, by attempting to restore the effects of the Neogene and eo-Alpine rotational events. The reconstruction gives a complex crustal-scale pattern in terms of dyke orientation, a fact that could be partly attributed to differential rotations associated with localized strike-slip movements that might have operated coevally with regional extension or transtension during Permian times.

  5. Litter decomposition over broad spatial and long time scales investigated by advanced solid-state NMR: insight into effects of climate, litter quality, and time

    Science.gov (United States)

    Mao, J.; Chen, N.; Harmon, M. E.; Li, Y.; Cao, X.; Chappell, M.

    2012-12-01

    Advanced 13C solid-state NMR techniques were employed to study the chemical structural changes of litter decomposition across broad spatial and long time scales. The fresh and decomposed litter samples of four species (Acer saccharum (ACSA), Drypetes glauca (DRGL), Pinus resinosa (PIRE), and Thuja plicata (THPL)) incubated for up to 10 years at four sites under different climatic conditions (from Arctic to tropical forest) were examined. Decomposition generally led to an enrichment of cutin and surface wax materials, and a depletion of carbohydrates causing overall composition to become more similar compared with original litters. However, the changes of main constituents in the four litters were inconsistent with the four litters following different pathways of decomposition at the same site. As decomposition proceeded, waxy materials decreased at the early stage and then gradually increased in PIRE; DRGL showed a significant depletion of lignin and tannin while the changes of lignin and tannin were relative small and inconsistent for ACSA and THPL. In addition, the NCH groups, which could be associated with either fungal cell wall chitin or bacterial wall petidoglycan, were enriched in all litters except THPL. Contrary to the classic lignin-enrichment hypothesis, DRGL with low-quality C substrate had the highest degree of composition changes. Furthermore, some samples had more "advanced" compositional changes in the intermediate stage of decomposition than in the highly-decomposed stage. This pattern might be attributed to the formation of new cross-linking structures, that rendered substrates more complex and difficult for enzymes to attack. Finally, litter quality overrode climate and time factors as a control of long-term changes of chemical composition.

  6. Patterns of scheduled follow-up appointments following hospitalization for heart failure: insights from an urban medical center in the United States

    Science.gov (United States)

    Goyal, Parag; Sterling, Madeline R; Beecy, Ashley N; Ruffino, John T; Mehta, Sonal S; Jones, Erica C; Lachs, Mark S; Horn, Evelyn M

    2016-01-01

    Objectives Although postdischarge outpatient follow-up appointments after a hospitalization for heart failure represent a potentially effective strategy to prevent heart failure readmissions, patterns of scheduled follow-up appointments upon discharge are poorly described. We aimed to characterize real-world patterns of scheduled follow-up appointments among adult patients with heart failure upon hospital discharge. Patients and methods This was a retrospective cohort study performed at a large urban academic center in the United States among adults hospitalized with a principal diagnosis of congestive heart failure between January 1, 2013, and December 31, 2014. Patient demographics, administrative data, clinical parameters, echocardiographic indices, and scheduled postdischarge outpatient follow-up appointments were collected. Results Of the 796 patients hospitalized for heart failure, just over half of the cohort had a scheduled follow-up appointment upon discharge. Follow-up appointments were less likely among patients who were white and had heart failure with preserved ejection fraction and more likely among patients with Medicaid and chronic obstructive pulmonary disease. In an adjusted multivariable regression model, age ≥65 years was inversely associated with a scheduled follow-up appointment upon hospital discharge, despite higher rates of several cardiovascular and noncardiovascular comorbidities. Conclusion Just half of the patients discharged home following a hospitalization for heart failure had a follow-up appointment scheduled, representing a missed opportunity to provide a recommended care transition intervention. Despite a greater burden of both cardiovascular and noncardiovascular comorbidities, older adults (age ≥65 years) were less likely to have a follow-up appointment scheduled upon discharge compared with younger adults, revealing a disparity that warrants further investigation. PMID:27713623

  7. Ground-state kinetics of bistable redox-active donor-acceptor mechanically interlocked molecules.

    Science.gov (United States)

    Fahrenbach, Albert C; Bruns, Carson J; Li, Hao; Trabolsi, Ali; Coskun, Ali; Stoddart, J Fraser

    2014-02-18

    The ability to design and confer control over the kinetics of theprocesses involved in the mechanisms of artificial molecular machines is at the heart of the challenge to create ones that can carry out useful work on their environment, just as Nature is wont to do. As one of the more promising forerunners of prototypical artificial molecular machines, chemists have developed bistable redox-active donor-acceptor mechanically interlocked molecules (MIMs) over the past couple of decades. These bistable MIMs generally come in the form of [2]rotaxanes, molecular compounds that constitute a ring mechanically interlocked around a dumbbell-shaped component, or [2]catenanes, which are composed of two mechanically interlocked rings. As a result of their interlocked nature, bistable MIMs possess the inherent propensity to express controllable intramolecular, large-amplitude, and reversible motions in response to redox stimuli. In this Account, we rationalize the kinetic behavior in the ground state for a large assortment of these types of bistable MIMs, including both rotaxanes and catenanes. These structures have proven useful in a variety of applications ranging from drug delivery to molecular electronic devices. These bistable donor-acceptor MIMs can switch between two different isomeric states. The favored isomer, known as the ground-state co-conformation (GSCC) is in equilibrium with the less favored metastable state co-conformation (MSCC). The forward (kf) and backward (kb) rate constants associated with this ground-state equilibrium are intimately connected to each other through the ground-state distribution constant, KGS. Knowing the rate constants that govern the kinetics and bring about the equilibration between the MSCC and GSCC, allows researchers to understand the operation of these bistable MIMs in a device setting and apply them toward the construction of artificial molecular machines. The three biggest influences on the ground-state rate constants arise from

  8. A Case Study of the Librarian-Initiated Publications Discovery Activities in State Level Digital Depositories in the United States

    Directory of Open Access Journals (Sweden)

    Chi-Shiou Lin

    2008-12-01

    Full Text Available This article describes the novel phenomenon of librarian-initiated publications discovery (LIPD in state-level digital depositories in the United States. LIPD is a series of actions taken by digital depository librarians to discover and inspect government Web sites and select Web content qualifying as government publications for inclusion in the state depositories. In a current popular model in which states employ OCLC Digital Archive™ for the depositories, the power of content selection has shifted from government agencies (content producers to digital depositories. This study systematically documented and compared the LIPD actions in four case states and developed a LIPD process model for descriptive and analytic purposes. It also discusses the impacts and challenges facing the changing practices in preserving government information as historical record. [Article content in Chinese

  9. Auditory Power-Law Activation Avalanches Exhibit a Fundamental Computational Ground State

    Science.gov (United States)

    Stoop, Ruedi; Gomez, Florian

    2016-07-01

    The cochlea provides a biological information-processing paradigm that we are only beginning to understand in its full complexity. Our work reveals an interacting network of strongly nonlinear dynamical nodes, on which even a simple sound input triggers subnetworks of activated elements that follow power-law size statistics ("avalanches"). From dynamical systems theory, power-law size distributions relate to a fundamental ground state of biological information processing. Learning destroys these power laws. These results strongly modify the models of mammalian sound processing and provide a novel methodological perspective for understanding how the brain processes information.

  10. Management and climate contributions to satellite-derived active fire trends in the contiguous United States

    Science.gov (United States)

    Lin, Hsiao-Wen; McCarty, Jessica L.; Wang, Dongdong; Rogers, Brendan M.; Morton, Douglas C.; Collatz, G. James; Jin, Yufang; Randerson, James T.

    2014-04-01

    Fires in croplands, plantations, and rangelands contribute significantly to fire emissions in the United States, yet are often overshadowed by wildland fires in efforts to develop inventories or estimate responses to climate change. Here we quantified decadal trends, interannual variability, and seasonality of Terra Moderate Resolution Imaging Spectroradiometer (MODIS) observations of active fires (thermal anomalies) as a function of management type in the contiguous U.S. during 2001-2010. We used the Monitoring Trends in Burn Severity database to identify active fires within the perimeter of large wildland fires and land cover maps to identify active fires in croplands. A third class of fires defined as prescribed/other included all residual satellite active fire detections. Large wildland fires were the most variable of all three fire types and had no significant annual trend in the contiguous U.S. during 2001-2010. Active fires in croplands, in contrast, increased at a rate of 3.4% per year. Cropland and prescribed/other fire types combined were responsible for 77% of the total active fire detections within the U.S and were most abundant in the south and southeast. In the west, cropland active fires decreased at a rate of 5.9% per year, likely in response to intensive air quality policies. Potential evaporation was a dominant regulator of the interannual variability of large wildland fires, but had a weaker influence on the other two fire types. Our analysis suggests it may be possible to modify landscape fire emissions within the U.S. by influencing the way fires are used in managed ecosystems.

  11. Characteristics and degradation of carbon and phosphorus from aquatic macrophytes in lakes: Insights from solid-state {sup 13}C NMR and solution {sup 31}P NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shasha [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Zhu, Yuanrong, E-mail: zhuyuanrong07@mails.ucas.ac.cn [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Meng, Wei, E-mail: mengwei@craes.org.cn [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); He, Zhongqi [USDA-ARS Southern Regional Research Center, 1100 Robert E Lee Blvd, New Orleans, LA 70124 (United States); Feng, Weiying [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Zhang, Chen [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Giesy, John P. [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan (Canada)

    2016-02-01

    Water extractable organic matter (WEOM) derived from macrophytes plays an important role in biogeochemical cycling of nutrients, including carbon (C), nitrogen (N) and phosphorus (P) in lakes. However, reports of their composition and degradation in natural waters are scarce. Therefore, compositions and degradation of WEOM derived from six aquatic macrophytes species of Tai Lake, China, were investigated by use of solid-state {sup 13}C NMR and solution {sup 31}P NMR spectroscopy. Carbohydrates were the predominant constituents of WEOM fractions, followed by carboxylic acid. Orthophosphate (ortho-P) was the dominant form of P (78.7% of total dissolved P) in the water extracts, followed by monoester P (mono-P) (20.6%) and little diester P (0.65%). The proportion of mono-P in total P species increased with the percentage of O-alkyl and O–C–O increasing in the WEOM, which is likely due to degradation and dissolution of biological membranes and RNA from aquatic plants. Whereas the proportion of mono-P decreased with alkyl-C, NCH/OCH{sub 3} and COO/N–C=O increasing, which may be owing to the insoluble compounds including C functional groups of alkyl-C, NCH/OCH{sub 3} and COO/N–C=O, such as aliphatic biopolymers, lignin and peptides. Based on the results of this study and information in the literature about water column and sediment, we propose that WEOM, dominated by polysaccharides, are the most labile and bioavailable component in debris of macrophytes. Additionally, these WEOMs would also be a potential source for bioavailable organic P (e.g., RNA, DNA and phytate) for lakes. - Highlights: • WEOM derived from aquatic macrophytes was characterized. • C and P in WEOM were characterized by solid {sup 13}C NMR and solution {sup 31}P NMR. • Degradation and transformation of macrophyte-derived C and P were investigated. • Macrophyte-derived WEOM are important source for bioavailable nutrients in lakes.

  12. Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010).

    Science.gov (United States)

    Gawron, Andrew J; Feinglass, Joseph; Pandolfino, John E; Tan, Bruce K; Bove, Michiel J; Shintani-Smith, Stephanie

    2015-01-01

    Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25-44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits

  13. Patterns of scheduled follow-up appointments following hospitalization for heart failure: insights from an urban medical center in the United States

    Directory of Open Access Journals (Sweden)

    Goyal P

    2016-09-01

    Full Text Available Parag Goyal,1 Madeline R Sterling,2 Ashley N Beecy,2 John T Ruffino,2 Sonal S Mehta,3 Erica C Jones,1 Mark S Lachs,3 Evelyn M Horn1 1Division of Cardiology, Department of Medicine, 2Department of Medicine, 3Division of Geriatrics, Department of Medicine, Weill Cornell Medicine, New York, NY, USA Objectives: Although postdischarge outpatient follow-up appointments after a hospitalization for heart failure represent a potentially effective strategy to prevent heart failure readmissions, patterns of scheduled follow-up appointments upon discharge are poorly described. We aimed to characterize real-world patterns of scheduled follow-up appointments among adult patients with heart failure upon hospital discharge.Patients and methods: This was a retrospective cohort study performed at a large urban academic center in the United States among adults hospitalized with a principal diagnosis of congestive heart failure between January 1, 2013, and December 31, 2014. Patient demographics, administrative data, clinical parameters, echocardiographic indices, and scheduled postdischarge outpatient follow-up appointments were collected.Results: Of the 796 patients hospitalized for heart failure, just over half of the cohort had a scheduled follow-up appointment upon discharge. Follow-up appointments were less likely among patients who were white and had heart failure with preserved ejection fraction and more likely among patients with Medicaid and chronic obstructive pulmonary disease. In an adjusted multivariable regression model, age ≥65 years was inversely associated with a scheduled follow-up appointment upon hospital discharge, despite higher rates of several cardiovascular and noncardiovascular comorbidities.Conclusion: Just half of the patients discharged home following a hospitalization for heart failure had a follow-up appointment scheduled, representing a missed opportunity to provide a recommended care transition intervention. Despite a greater

  14. Metagenomics, single cell genomics, and steady-state free energy flux provide insight into the biogeochemical cycling of deep, meteoric water

    Science.gov (United States)

    Magnabosco, C.; Lau, C. M.; Ryan, K.; Kieft, T. L.; Snyder, L.; Sherwood Lollar, B.; Lacrampe Couloume, G.; Hendrickson, S.; Pullin, M. J.; Slater, G. F.; Simkus, D.; Borgonie, G.; van Heerden, E.; Kuloyo, O.; Maleke, M.; Tlalajoe, T.; Vermeulen, J.; Vermeulen, F.; Munro, A.; Pienaar, M.; Stepanauskas, R.; Grim, S. L.; Onstott, T. C.

    2013-12-01

    Prior to the onset of high-throughput sequencing, the study of biogeochemical cycling in the terrestrial deep subsurface was limited to geochemical, thermodynamic, culture dependent microbial and low-throughput molecular analyses. Here, we present an integration of these traditional methods with high-throughput metagenomic and single cell analysis of 3.1 km deep water collected from a borehole (TT107) located in AngloGold Ashanti's TauTona Au Mine of South Africa and intersecting a fracture within a Witwatersrand Supergroup quartzite. The low salinity fracture water encountered at this depth is meteoric in origin and has a subsurface residence time on the order of a few thousand years. Aqueous geochemistry and estimated steady-state free energy flux values suggest that redox reactions are driven by the oxidation of abundant, energy-rich substrates including H2, CO, CH4, formate, and propanoate. The majority of the metagenome's sequences related to the phyla Firmicutes and Proteobacteria, which contain several bacterial species that are likely to exhibit chemoautotrophic metabolism. Sequence data confirms that many of these bacteria have the ability reduce of sulfur and nitrogen species via dissimilatory pathways. Thermincola were the most abundant firmicutes at this location and were sequenced at the single cell level. Notably, Thermincola sp. are capable of reducing metals and may utilize energy rich manganese reduction pathways at TT107. The CH4 at this site is of abiological origin (δ13C-C1-3 = -43.5 to -44.3 VPDB; δ2H-C1-3 = -345 to -200 VSMOW) despite the metagenome containing several sequences that are closely related to methanogens in the archaeal phyla Euryarchaeota. Alternatively, these archaea may belong to a group of euryarchaetoa commonly referred to as anaerobic mehanotrophic archaea (ANME) - suggesting that anaerobic oxidation (AOM) of abiogenic CH4 coupled to the reduction of sulfate species may be occurring at this site. Sequences for pmoA and s

  15. Effect of immobilization support, water activity, and enzyme ionization state on cutinase activity and enantioselectivity in organic media.

    Science.gov (United States)

    Vidinha, Pedro; Harper, Neil; Micaelo, Nuno M; Lourenco, Nuno M T; da Silva, Marco D R Gomes; Cabral, Joaquim M S; Afonso, Carlos A M; Soares, Claudio M; Barreiros, Susana

    2004-02-20

    We studied the reaction between vinyl butyrate and 2-phenyl-1-propanol in acetonitrile catalyzed by Fusarium solani pisi cutinase immobilized on zeolites NaA and NaY and on Accurel PA-6. The choice of 2-phenyl-1-propanol was based on modeling studies that suggested moderate cutinase enantioselectivity towards this substrate. With all the supports, initial rates of transesterification were higher at a water activity (a(w)) of 0.2 than at a(w) = 0.7, and the reverse was true for initial rates of hydrolysis. By providing acid-base control in the medium through the use of solid-state buffers that control the parameter pH-pNa, which we monitored using an organo-soluble chromoionophoric indicator, we were able, in some cases, to completely eliminate dissolved butyric acid. However, none of the buffers used were able to improve the rates of transesterification relative to the blanks (no added buffer) when the enzyme was immobilized at an optimum pH of 8.5. When the enzyme was immobilized at pH 5 and exhibited only marginal activity, however, even a relatively acidic buffer with a pK(a) of 4.3 was able to restore catalytic activity to about 20% of that displayed for a pH of immobilization of 8.5, at otherwise identical conditions. As a(w) was increased from 0.2 to 0.7, rates of transesterification first increased slightly and then decreased. Rates of hydrolysis showed a steady increase in that a(w) range, and so did total initial reaction rates. The presence or absence of the buffers did not impact on the competition between transesterification and hydrolysis, regardless of whether the butyric acid formed remained as such in the reaction medium or was eliminated from the microenvironment of the enzyme through conversion into an insoluble salt. Cutinase enantioselectivity towards 2-phenyl-1-propanol was indeed low and was not affected by differences in immobilization support, enzyme protonation state, or a(w).

  16. Activated and deactivated functional brain areas in the Deqi state A functional MRI study

    Institute of Scientific and Technical Information of China (English)

    Yong Huang; Tongjun Zeng; Guifeng Zhang; Ganlong Li; Na Lu; Xinsheng Lai; Yangjia Lu; Jiarong Chen

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state,as reported by physicians and subjects during acupuncture.Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint.Real-time cerebral functional MRI showed that compared with non-sensation after sham needling,true needling activated Brodmann areas 3,6,8,9,10,11,13,20,21,37,39,40,43,and 47,the head of the caudate nucleus,the parahippocampal gyrus,thalamus and red nucleus.True needling also deactivated Brodmann areas 1,2,3,4,5,6,7,9,10,18,24,31,40 and 46.

  17. The steady-state performance of a controlled current active filter

    Energy Technology Data Exchange (ETDEWEB)

    Duke, R.M. (Univ. of Canterbury, Christchurch (New Zealand). Dept. of Electrical and Electronic Engineering); Round, S.D. (Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Electrical Engineering)

    1993-04-01

    An active filter that uses a high-frequency D-class asynchronous switching inverter for power system current distortion compensation is described. The distortion compensation technique involves deriving a signal corresponding to the distortion component of load current, and inverting and amplifying this signal for addition back to the supply current to cancel the load current distortion. A synthetic sinusoid is used to determine the distortion component in the time domain. Extensive computed and experimental results, illustrating the system's steady-state performance and ability to reduce the current harmonic distortion components, are presented. An intelligent controller is proposed to maintain the active filter's performance at the optimal operating point under varying load conditions.

  18. State space approach for joint estimation of activity and attenuation map from PET emission sinograms

    Institute of Scientific and Technical Information of China (English)

    Liu Huafeng; You Hongshun; Shi Pengcheng

    2007-01-01

    Quantitative estimation of radioactivity map has important clinical implications for better diagnosis and understanding of cancers. Although attenuation map and activity map are usually treated sequentially, they can obviously benefit a great deal when the transmission data is missing. In this paper, we propose a novel scheme of simultaneously solving for attenuation map and activity distribution from emission sinograms. Our strategy combines the measurement model of PET, and the attenuation parameters are treated as random variables with known prior statistics. After the conversion to state space representation, the extended Kalman filtering procedures are adopted to linearize the equations and to provide the joint estimates in an approximate optimal sense. Experiments have been performed on both synthetic data to illustrate its abilities and benefits.

  19. State of the art review of semi active control for magnetorheological dampers

    Science.gov (United States)

    Mughal, Umair Najeeb

    2017-01-01

    Earthquakes causes severe damage to badly designed structures or buildings to fail or collapse, and also have caused some damage to well-designed structures to malfunction due to the damage or failure of the equipment housed in the structure or building. The use magnetorheological dampers to mitigate the effect of external excitation is increased to resolve this. This article is a state of the art review of nonlinear analytical models to understand the efficacy of semi-active control theory for magnetorheological dampers. A nonlinear semi active control law is desired to be designed which atleast guarantees analytical closed loop stability in order to mitigate the effect of perturbations and drive the desired output to equilibrium.

  20. Demonstration of intuitive thinking in conditions of competitive activity depending on athletes' psychophysiological state.

    Directory of Open Access Journals (Sweden)

    Korobeynikov G.V.

    2012-07-01

    Full Text Available One investigated application of intuitive thinking, depending on the physiological status of skilled fighters in their competitive activity. In research members of the team of Ukraine in Greco-Roman wrestling participated. 29 effective throws were analysed reverse a capture from position orchestra. One analyzed the effectiveness of intuitive thinking in athletes of different weight categories and the distribution coefficients of correlation of psychophysiological functions of athletes directly in competition during championships of Ukraine, World and Europe. One found that expression of intuitive thinking is associated with weight category of skilled fighters. It is shown that the effectiveness of intuitive thinking in terms of competitive activity is related to physiological state, and, above all qualified wrestlers' neurodynamic functions.

  1. Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Klein-Seetharaman Judith

    2008-02-01

    Full Text Available Abstract Metabotropic glutamate receptors (mGluRs are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is experimentally known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. We find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%, the negative modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%, the positive modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86% and 8/9 (89% for ArgusLab and 10/14 (71% and 7/9 (78% for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by

  2. Aerosol mixing state, hygroscopic growth and cloud activation efficiency during MIRAGE 2006

    Directory of Open Access Journals (Sweden)

    S. Lance

    2013-05-01

    Full Text Available Observations of aerosol hygroscopic growth and CCN activation spectra for submicron particles are reported for the T1 ground site outside of Mexico City during the MIRAGE 2006 campaign. κ-Köhler theory is used to evaluate the characteristic hygroscopicity parameter, κ*, for the CCN active aerosol population using both size-resolved HTMDA and size-resolved CCNc measurements. Organic mass fractions (forg are evaluated from size-resolved aerosol mass spectrometer (AMS measurements, from which predictions of the hygroscopicity parameter are compared against κ*. Strong diurnal changes in aerosol water uptake parameters and aerosol composition are observed. We find that new particle formation (NPF events are correlated with an increased κ* and CCN-active fraction during the daytime, with greater impact on smaller particles. During NPF events, the number concentration of 40 nm particles acting as CCN at 0.51% ± 0.06% supersaturation can surpass by more than a factor of two the corresponding concentrations of 100 nm particles. We also find that at 06:00–08:00 LT throughout the campaign, fresh traffic emissions result in substantial changes to the chemical distribution of the aerosol, with on average 65% externally mixed fraction for 40 nm particles and 30% externally mixed fraction for 100 nm particles, whereas at midday nearly all particles of both sizes can be described as "internally mixed". Average activation spectra and growth factor distributions are analyzed for different time periods characterizing the daytime (with and without NPF events, the early morning "rush hour" and the entire campaign. We show that κ* derived from CCNc measurements decreases as a function of size during all time periods, while the CCN-active fraction increases as a function of size. Size-resolved AMS measurements do not predict the observed trend for κ* versus particle size, which can be attributed to unresolved mixing state and the presence of refractory

  3. Estrogen modification of human glutamate dehydrogenases is linked to enzyme activation state.

    Science.gov (United States)

    Borompokas, Nikolas; Papachatzaki, Maria-Martha; Kanavouras, Konstantinos; Mastorodemos, Vasileios; Zaganas, Ioannis; Spanaki, Cleanthe; Plaitakis, Andreas

    2010-10-08

    Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC(50) = 0.1-0.3 μM) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC(50) = 0.08 ± 0.01 μM) and with ∼18-fold lower affinity hGDH1 (IC(50) = 1.67 ± 0.06 μM; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC(50) = 1.53 ± 0.24 μM) than for hGDH1 (IC(50) = 26.94 ± 1.07 μM; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain.

  4. State and evolution of the Bérard rock glacier (Southern French Alps) after its collapse in 2006: insights from geophysical, geodetic and thermal datasets

    Science.gov (United States)

    Krysiecki, Jean-Michel; Le Roux, Olivier; Bodin, Xavier; Schoeneich, Philippe

    2010-05-01

    In the French Alps, the summer 2006 has been marked by the sudden collapse of the Bérard rockglacier, a rare event, exceptional by the quasi complete destabilization of the landform. This case raises questions on the evolution of mountain permafrost under warming conditions, especially those ice-rich debris accumulations located close to the altitudinal and/or latitudinal limits of permafrost and that may be experiencing morphogenetic crisis. The Bérard site (2500-2900 m asl; 44°26' N. - 6°40' E.) is located in the Parpaillon range, near the Southern limits of the Alpine permafrost and under Mediterranean climatic conditions. The objectives of our study are to analyse the present state of the Bérard rock glacier (collapsed and non-collapsed mass) and its evolution after the major movements of summer 2006 that mobilized 1.5 millions m3 of material. In this purpose, electrical resistivity and seismic refraction tomographies were repeated along two profiles in summers 2007 and 2009, GPS survey of 40 points was initiated in summer 2007 and a thermal monitoring, composed of 6 miniature temperature dataloggers and an automatic weather station was installed on the site on summer 2007. First, the combination of the thermal and geodetic data allows us to distinguish three areas: 1) the unstable but non-collapsed upper part of the rock glacier, characterized by creeping signs and which displays surface velocity between 0.1 and 0.6 m/yr and WEqT (Winter Equilibrium Temperature) values > - 2°C in 2008 and 2009; 2) the highly unstable but non-collapsed median part, characterized by destabilization signs like wide fractures and which displays surface velocity up to 8 m/yr (no ground temperature available); 3) the collapsed mass, characterized by strong morphological changes (rapid downwasting of ice/debris packets) just after the deposition but no visible signs of evolution since 2007 and which displays surface velocity below 0.1 m/yr and WEqT around 0°C. The electrical

  5. Older but still fluent? Insights from the intrinsically active baseline configuration of the aging brain using a data driven graph-theoretical approach.

    Science.gov (United States)

    Muller, Angela M; Mérillat, Susan; Jäncke, Lutz

    2016-02-15

    A major part of our knowledge about the functioning of the aging brain comes from task-induced activation paradigms. However, the aging brain's intrinsic functional organization may be already a limiting factor for the outcome of an actual behavior. In order to get a better understanding of how this functional baseline configuration of the aging brain may affect cognitive performance, we analyzed task-free fMRI data of older 186 participants (mean age=70.4, 97 female) and their performance data in verbal fluency: First, we conducted an intrinsic connectivity contrast analysis (ICC) for the purpose of evaluating the brain regions whose degree of connectedness was significantly correlated with fluency performance. Secondly, using connectivity analyses we investigated how the clusters from the ICC functionally related to the other major resting-state networks. Apart from the importance of intact fronto-parietal long-range connections, the preserved capacity of the DMN for a finely attuned interaction with the executive-control network and the language network seems to be crucial for successful verbal fluency performance in older people. We provide further evidence that the right frontal regions might be more prominently affected by age-related decline.

  6. Toward a comprehensive model for feedback by active galactic nuclei: new insights from M87 observations by LOFAR, Fermi and H.E.S.S

    CERN Document Server

    ,

    2013-01-01

    Feedback by active galactic nuclei (AGN) appears to be critical in balancing radiative cooling of the low-entropy gas at the centers of galaxy clusters and in mitigating the star formation of elliptical galaxies. New observations of M87 enable us to put forward a comprehensive model for the physical heating mechanism. Low-frequency radio observations by LOFAR revealed the absence of fossil cosmic ray (CR) electrons in the radio halo surrounding M87. This puzzle can be resolved by accounting for the CR release from the radio cocoons and the subsequent mixing of CRs with the dense ambient intracluster gas, which thermalizes the electrons on a timescale similar to the radio halo age of 40 Myrs. Hadronic interactions of similarly injected CR protons with the ambient gas should produce an observable gamma-ray signal in accordance with the steady emission of the low state of M87 detected by Fermi and H.E.S.S. Hence, we normalize the CR population to the gamma-ray emission, which shows the same spectral slope as the...

  7. An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo.

    Directory of Open Access Journals (Sweden)

    Cleopatra Kozlowski

    Full Text Available Microglia are specialized immune cells of the brain. Upon insult, microglia initiate a cascade of cellular responses including a characteristic change in cell morphology. To study the dynamics of microglia immune response in situ, we developed an automated image analysis method that enables the quantitative assessment of microglia activation state within tissue based solely on cell morphology. Per cell morphometric analysis of fluorescently labeled microglia is achieved through local iterative threshold segmentation, which reduces errors caused by signal-to-noise variation across large volumes. We demonstrate, utilizing systemic application of lipopolysaccharide as a model of immune challenge, that several morphological parameters, including cell perimeter length, cell roundness and soma size, quantitatively distinguish resting versus activated populations of microglia within tissue comparable to traditional immunohistochemistry methods. Furthermore, we provide proof-of-concept data that monitoring soma size enables the longitudinal assessment of microglia activation in the mouse neocortex imaged via 2-photon in vivo microscopy. The ability to quantify microglia activation automatically by shape alone allows unbiased and rapid analysis of both fixed and in vivo central nervous system tissue.

  8. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2016-08-01

    Full Text Available Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA, using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA’s influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence—influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.

  9. State observer-based sliding mode control for semi-active hydro-pneumatic suspension

    Science.gov (United States)

    Ren, Hongbin; Chen, Sizhong; Zhao, Yuzhuang; Liu, Gang; Yang, Lin

    2016-02-01

    This paper proposes an improved virtual reference model for semi-active suspension to coordinate the vehicle ride comfort and handling stability. The reference model combines the virtues of sky-hook with ground-hook control logic, and the hybrid coefficient is tuned according to the longitudinal and lateral acceleration so as to improve the vehicle stability especially in high-speed condition. Suspension state observer based on unscented Kalman filter is designed. A sliding mode controller (SMC) is developed to track the states of the reference model. The stability of the SMC strategy is proven by means of Lyapunov function taking into account the nonlinear damper characteristics and sprung mass variation of the vehicle. Finally, the performance of the controller is demonstrated under three typical working conditions: the random road excitation, speed bump road and sharp acceleration and braking. The simulation results indicated that, compared with the traditional passive suspension, the proposed control algorithm can offer a better coordination between vehicle ride comfort and handling stability. This approach provides a viable alternative to costlier active suspension control systems for commercial vehicles.

  10. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States.

    Science.gov (United States)

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-08-17

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.

  11. STUDIES ON THE CHEMICAL STRUCTURES OF ACTIVATED CARBON FIBERS BY SOLID STATE NMR

    Institute of Scientific and Technical Information of China (English)

    FURuowen; HuangWenqiang; 等

    1999-01-01

    The solid state C13-NMR spectra of different ACFs from various precursor fibers were recorded in this paper,The effects of activation conditions on chemical structures of ACFs,as well as the changes of chemical structures during carbonization and redox reaction were inverstigated by NMR technique,At same time,the soild state P31-NMR spectra of ACFS are studied.The C13-NMR spectra of ACFs can be divided into six bands that are assigned to methyl and methylene groups,hydroxyl and ether groups.acetal (or methylenedioxy) carbon,graphite-like aromatic carbon structure,phenol,and quinone groups,respectively.Only phosphorous pentoxide exists on ACFs and CFs.Moreover,most of them are stuck over the crystal face but not at the edge of graphite-like micro-crystal.The carbonization and activation conditions affect the C13-NMR spectra of ACFs.The experimental rsults indicate that the redox reaction of ACFs with oxidants greatly consumes C-H group.

  12. Microwave heating enhances antioxidant and emulsifying activities of ovalbumin glycated with glucose in solid-state.

    Science.gov (United States)

    Tu, Zong-Cai; Hu, Yue-Ming; Wang, Hui; Huang, Xiao-Qin; Xia, Shi-Qi; Niu, Pei-Pei

    2015-03-01

    The aim of this study was to characterize the properties of ovalbumin (OVA) after glycated with glucose under microwave heating. For this purpose, microwave at 480 and 640 W power levels were used for heating the OVA-glucose system in solid-state for 0, 5, 10, 15, 20 and 25 min, respectively. The results indicated that the protein molecular weight was increased after glycated with glucose under microwave treatment, the pH of the system was decreased with the increase of microwave treatment power and time, while the UV absorbance, browning intensity, antioxidant activities as well as the emulsifying activity and emulsion stability of the Maillard reaction products (MRPs) were increased in according with the raise of microwave treatment power and time. The reaction time of microwave treatment is much shorter than those using traditional methods, suggesting that microwave irradiation is a novel and efficient approach to promote Maillard reaction (MR) in dry state and improve protein antioxidant and functional properties.

  13. Altered regional and circuit resting-state activity associated with unilateral hearing loss.

    Directory of Open Access Journals (Sweden)

    Xingchao Wang

    Full Text Available The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI, the key node of cognitive control network (CCN and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC, a key node in the default mode network (DMN. Moreover, seed-based resting-state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network.

  14. Intrinsic brain activity in altered states of consciousness: how conscious is the default mode of brain function?

    Science.gov (United States)

    Boly, M; Phillips, C; Tshibanda, L; Vanhaudenhuyse, A; Schabus, M; Dang-Vu, T T; Moonen, G; Hustinx, R; Maquet, P; Laureys, S

    2008-01-01

    Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto-cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level-dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark.

  15. The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

    Science.gov (United States)

    Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

    2016-02-01

    Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity.

  16. New insight into the enhanced visible-light photocatalytic activities of B-, C- and B/C-doped anatase TiO2 by first-principles.

    Science.gov (United States)

    Yu, Jiaguo; Zhou, Peng; Li, Qin

    2013-08-07

    The geometry structures, formation energies and electronic properties of the B-, C- and B/C-doped anatase TiO2 were investigated by the density functional theory (DFT) calculations of first-principles. The results indicated that the visible-light absorption and photocatalytic activities of the B-, C- and B/C-doped anatase TiO2 were not only influenced by the energy gaps (Eg) and the distributions of impurity states, but also affected by the locations of Fermi levels (EF) and the energies of the edges of band gaps (Ev for the top of valence bands and Ec for the bottom of conduction bands). However, the above four factors changed with the doped models of TiO2. The impurity states in the band gaps reduced the maximum energy gaps in the band gaps, which is responsible for the absorption of visible light. The Fermi levels at the bottom of conduction bands indicated the existence of Ti(3+) ions, which enhanced the separation rates of photogenerated electrons and holes. Further, the energies of the edges of band gaps, determining the dominant types of oxidants (O2(-), hole, ˙OH) in the photocatalytic degradation, were discussed. Moreover, the stability of the doped TiO2 depended on its growth conditions (O-rich or Ti-rich environment). The O-rich growth condition is beneficial to the substitutional B and C atoms to Ti atoms, while the Ti-rich growth condition is favorable to the other doped TiO2 including the most stable co-doped TiO2 with the interstitial B atom and the substitutional C atom to O atom. In addition, our results also showed that the B/C-doped TiO2 inherited the partial electronic properties of single-doped TiO2, but also exhibited many new electronic properties, implying that the electronic properties of co-doped systems are not a mechanical mixture of those of both single-doped systems.

  17. Antimicrobial activity from endophytic fungi Arthrinium state of Apiospora montagnei Sacc. and Papulaspora immersa

    Directory of Open Access Journals (Sweden)

    Henrique Pereira Ramos

    2010-06-01

    Full Text Available Papulaspora immersa and Arthrinium state of Apiospora montagnei Sacc. were isolated from the roots of Smallanthus sonchifolius (yacón. The crude extracts from their cultures inhibited the growth of Staphylococcus aureus, Kocuria rhizophila, Pseudomonas aeruginosa and Escherichia coli. The more relevant results were observed in the ethyl acetate extract from P immersa against P aeruginosa (90 µg/mL and ethyl acetate extract from Arthrinium state of A montagnei Sacc. against P aeruginosa (160 µg/mL. The two endophytic fungi isolated from yacón roots as well as their antimicrobial activity detected in the crude extracts cultures were being reported for the first time.Mesmo havendo grandes investimentos, a resistência a fármacos continua sendo um grave problema de saúde pública. Produtos naturais têm prevalecido como a maior fonte de novas drogas e muitos deles são isolados de sistemas simbióticos: microorganismos-plantas. Os fungos endofíticos Papulaspora immersa e Arthrinium state of Apiospora montagnei Sacc. foram isolados de raízes de Smallanthus sonchifolius (yacón. Extratos de culturas destes fungos apresentaram atividade antibacteriana frente Staphylococcus aureus, Kocuria rhizophila, Pseudomonas aeruginosa e Escherichia coli, sendo as mais relevantes observadas nas frações acetato de etila provenientes dos fungos P. immersa e Arthrinium state of Apiospora montagnei Sacc. frente a P. aeruginosa, apresentando CIM de 90µg/mL e 160µg/mL, respectivamente.

  18. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model.

    Science.gov (United States)

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The "paradoxically" high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception.

  19. Macrophages driven to a novel state of activation have anti-inflammatory properties in mice.

    Science.gov (United States)

    Brem-Exner, Beate G; Sattler, Christine; Hutchinson, James A; Koehl, Gudrun E; Kronenberg, Katharina; Farkas, Stefan; Inoue, Seiichiro; Blank, Christian; Knechtle, Stuart J; Schlitt, Hans J; Fändrich, Fred; Geissler, Edward K

    2008-01-01

    Recurrent episodes of inflammation underlie numerous pathologies, notably those of inflammatory bowel diseases. In this study, we describe a population of macrophages in a novel state of activation that mitigates colitis in mice. The cells responsible for this effect, called IFN-gamma-stimulated monocyte-derived cells (IFNgamma-MdC), derive from mouse spleen, blood, and bone marrow monocytes and are distinguished from known macrophage populations by mode of generation, cell surface phenotype, and function. IFNgamma-MdC only arise when macrophages are cultivated in the presence of CD40L-expressing CD4+ T cells, M-CSF, and IFN-gamma. IFNgamma-MdC express markers including F4/80, CD11b/c, CD86, and CD274; they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally, IFNgamma-MdC are defined by their capacity to enrich cocultured T cell populations for CD4+CD25+Foxp3+ regulatory cells; this enrichment, constituting up to 60% or more of residual lymphocytes, is attributed to an expansion, but also to a cell contact and caspase-dependent depletion of activated T cells. In mice, IFNgamma-MdC delivered i.v. traffic to gut-associated peripheral lymphoid tissues, including the mesenteric lymph nodes, Peyer's patches, and colonic mucosa, and promote the clinical and histological resolution of chronic colitis. We conclude that IFNgamma-MdC represent macrophages in a novel state of activation, possessing multiple T cell-suppressive effects with therapeutic potential for the treatment of autoimmune inflammation.

  20. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

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    Kazuhito eNakao

    2014-07-01

    Full Text Available In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 sec, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1 a broadband increase in spontaneous LFP power in the absence of external inputs, and (2 a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The paradoxically high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception.

  1. Resting-state oscillatory activity in children born small for gestational age: a magnetoencephalographic study

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    Maria eBoersma

    2013-09-01

    Full Text Available Growth restriction in utero during a period that is critical for normal growth of the brain, has previously been associated with deviations in cognitive abilities and brain anatomical and functional changes. We measured magnetoencephalography (MEG in 4-7 year old children to test if children born small for gestational age (SGA show deviations in resting-state brain oscillatory activity. Children born SGA children with postnatally spontaneous catch-up growth (SGA+; 6 boys, 7 girls; mean age 6.3 y (SD=0.9 and children born appropriate for gestational age (AGA; 7 boys, 3 girls; mean age 6.0 y (SD=1.2 participated in a resting-state MEG study. We calculated absolute and relative power spectra and used nonparametric statistics to test for group differences. SGA+ and AGA born children showed no significant differences in absolute and relative power except for reduced absolute gamma band power in SGA children. At time of MEG investigation, SGA+ children showed was significantly lower head circumference (HC and a trend toward lower IQ, however there was no association of HC or IQ with absolute or relative power. Except for reduced absolute gamma band power, our findings suggest normal brain activity patterns at school age in a group of children born SGA in which spontaneous catch-up growth of bodily length after birth occurred. Although previous findings suggest that being born SGA alters brain oscillatory activity early in neonatal life, we show that these neonatal alterations do not persist at early school age when spontaneous postnatal catch-up growth occurs after birth.

  2. Insight into both coverage and surface structure dependent CO adsorption and activation on different Ni surfaces from DFT and atomistic thermodynamics.

    Science.gov (United States)

    Hao, Xiaobin; Wang, Baojun; Wang, Qiang; Zhang, Riguang; Li, Debao

    2016-06-29

    CO adsorption and activation on Ni(100), (110) and (111) surfaces have been systematically investigated to probe the effect of coverage and surface structure on CO adsorption and activation. Herein, dispersion-corrected density functional theory calculations (DFT-D) were employed, and the related thermodynamic energies at 523 K were calculated by including the zero-point energy, thermal energy and entropic corrections; the results show that the saturated coverage of CO on the Ni(111), (100) and (110) surfaces correspond to 8/9, 9/12 and 9/9 ML, respectively. As the coverage increases, the stepwise adsorption free energies decrease on the flat (111) and (100) surfaces, whereas small changes occur on the corrugated (110) surface. CO migrates from the three-fold hollow site to the top site on the (111) surface, and from the four-fold hollow to the two-fold bridge site on the (100) surface, while all the CO molecules remain at the short-bridge site on the (110) surface. As a result, the obtained intermolecular CO-CO repulsive interactions on the flat surface are stronger than the interactions on the corrugated surface. Furthermore, the computed CO vibrational frequencies at different levels of coverage over the Ni surfaces agree well with the experimental results. On the other hand, kinetic analyses were utilized to compare the stepwise CO desorption with the dissociation at different degrees of coverage on the three Ni surfaces. CO desorption is more favorable than its dissociation at all coverage levels on the most exposed Ni(111) surface. Analogously, CO desorption becomes more favorable than its dissociation on the Ni(110) surface at higher coverage, except for coverage of 1/9 ML, in which CO desorption competes with its dissociation. However, on the Ni(100) surface, CO dissociation is more favorable than its desorption at 1/12 ML; when the coverage increases from 2/12 to 3/12 ML, equilibrium states exist between dissociation and desorption over the surface; when

  3. Metallomics for drug development: a further insight into intracellular activation chemistry of a ruthenium(III)-based anticancer drug gained using a multidimensional analytical approach.

    Science.gov (United States)

    Matczuk, Magdalena; Prządka, Monika; Aleksenko, Svetlana S; Czarnocki, Zbigniew; Pawlak, Katarzyna; Timerbaev, Andrei R; Jarosz, Maciej

    2014-01-01

    The mechanism by which the most relevant ruthenium anticancer drugs are activated in tumors to commence their tumor-inhibiting action remains one of the challenging research tasks of present-day metallomics. This contribution aims to capture and identify eventually more reactive species of one of two bis-indazole tetrachloridoruthenate(III) compounds that are progressing in clinical trials. In view of the fact that the transport of ruthenium into cancer cells is governed by transferrin receptors, the susceptibility of the Ru drug adduct with holo-transferrin to exposure by glutathione and ascorbic acid (at their cancer cytosol concentrations) was studied by inductively coupled plasma mass spectrometry (ICP-MS), following isolation of the reaction products by ultrafiltration. Next, capillary electrophoresis coupled to ICP-MS was applied to monitor changes in the Ru speciation both under simulated cancer cytosol conditions and in real cytosol and to assign the charge state of novel metal species. The latter were identified by using tandem electrospray ionization MS in the respective ion mode. The formation of ruthenium(II) species was for the first time revealed, in which the central metal is coordinated by the reduced (GSH) or the oxidized (GSSG) form of glutathione, i.e. [Ru(II)HindCl4(GSH)](2-) and [Ru(II)HindCl4(GSSG)](2-), respectively (Hind = indazole). Ascorbic acid released the ruthenium functionality from the protein-bound form in a different way, the products of adduct cleavage containing aqua ligands. Distribution of low-molecular mass species of Ru in human cytosol was found to have very much in common with the ruthenium speciation assayed under simulated cytosol conditions.

  4. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

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    Mojgan Masoodi

    Full Text Available OBJECTIVES: Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC. DESIGN: Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically. RESULTS: Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems. CONCLUSIONS: Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  5. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Science.gov (United States)

    2010-01-01

    ... foreign organization engages in the United States are incidental to its international or foreign business... representative office. (2) The following activities are incidental to international or foreign business: (i... INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  6. Plans for the development of infrastructure and tourism activities in landscape parks under the State Forests’ administration

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    Referowska-Chodak Ewa

    2015-12-01

    Full Text Available The aim of the study was to present plans (up to 2030 for the development of infrastructure and tourism activities in the Polish landscape parks located in the area of the State Forests’ administration.

  7. Theorems and Application of Local Activity of CNN with Five State Variables and One Port

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    Gang Xiong

    2012-01-01

    Full Text Available Coupled nonlinear dynamical systems have been widely studied recently. However, the dynamical properties of these systems are difficult to deal with. The local activity of cellular neural network (CNN has provided a powerful tool for studying the emergence of complex patterns in a homogeneous lattice, which is composed of coupled cells. In this paper, the analytical criteria for the local activity in reaction-diffusion CNN with five state variables and one port are presented, which consists of four theorems, including a serial of inequalities involving CNN parameters. These theorems can be used for calculating the bifurcation diagram to determine or analyze the emergence of complex dynamic patterns, such as chaos. As a case study, a reaction-diffusion CNN of hepatitis B Virus (HBV mutation-selection model is analyzed and simulated, the bifurcation diagram is calculated. Using the diagram, numerical simulations of this CNN model provide reasonable explanations of complex mutant phenomena during therapy. Therefore, it is demonstrated that the local activity of CNN provides a practical tool for the complex dynamics study of some coupled nonlinear systems.

  8. Influence of the emotional state on behavior in extreme conditions of competitive sports activities

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    Malakhov V.A.

    2014-03-01

    Full Text Available Purpose : establish a communication pattern of emotional intensity and level of extreme environment in which activity is performed. Materials : in the study involved 600 men aged 18-22 years. Results : the effect of the emotional state on the efficiency of the motor activity that flowed under extreme conditions. Set individual characteristics flow sports activities in extreme conditions. First used in the special semantic space for the orderly presentation of research results parachute jumps. The monogram built in semantic fields allows to establish the frequency response range of individual heartbeats and the optimal frequency for maximum performance. On the basis of established regularities of the "reflex of readiness" assessment methodology given emotional stress, which reflects the readiness of an individual to perform a parachute jump. An objective indicator of preparedness measures is a violation of the symmetry of the flow and haptic reflex and serial dynamometry. Conclusions : in using semantic spaces reflects the flowing of reflex of biological caution and accompaniment reflex. In the basis of constructing estimates of emotional stress are the regularities of mean arterial pressure as nonspecific reactions. Measure of extent of confused is estimated by variability of accompaniment reflex. Breach of symmetry in mean arterial pressure and the amplitude - frequency response accompaniment reflex, determine the validity of staying in extreme conditions. Introduction of the measure in using semantic spaces allows by selective data to establish the overall structure of the studied process.

  9. Large amplitude Fourier transformed AC voltammetric investigation of the active state electrochemistry of a copper/aqueous base interface and implications for electrocatalysis.

    Science.gov (United States)

    Shiddiky, Muhammad J A; O'Mullane, Anthony P; Zhang, Jie; Burke, L Declan; Bond, Alan M

    2011-08-16

    The higher harmonic components available from large-amplitude Fourier-transformed alternating current (FT-ac) voltammetry enable the surface active state of a copper electrode in basic media to be probed in much more detail than possible with previously used dc methods. In particular, the absence of capacitance background current allows low-level Faradaic current contributions of fast electron-transfer processes to be detected; these are usually completely undetectable under conditions of dc cyclic voltammetry. Under high harmonic FT-ac voltammetric conditions, copper electrodes exhibit well-defined and reversible premonolayer oxidation responses at potentials within the double layer region in basic 1.0 M NaOH media. This process is attributed to oxidation of copper adatoms (Cu*) of low bulk metal lattice coordination numbers to surface-bonded, reactive hydrated oxide species. Of further interest is the observation that cathodic polarization in 1.0 M NaOH significantly enhances the current detected in each of the fundamental to sixth FT-ac harmonic components in the Cu*/Cu hydrous oxide electron-transfer process which enables the underlying electron transfer processes in the higher harmonics to be studied under conditions where the dc capacitance response is suppressed; the results support the incipient hydrous oxide adatom mediator (IHOAM) model of electrocatalysis. The underlying quasi-reversible interfacial Cu*/Cu hydrous oxide process present under these conditions is shown to mediate the reduction of nitrate at a copper electrode, while the mediator for the hydrazine oxidation reaction appears to involve a different mediator or active state redox couple. Use of FT-ac voltammetry offers prospects for new insights into the nature of active sites and electrocatalysis at the electrode/solution interface of Group 11 metals in aqueous media.

  10. Composite Disease Activity and Responder Indices for Psoriatic Arthritis: A Report from the GRAPPA 2013 Meeting on Development of Cutoffs for Both Disease Activity States and Response

    NARCIS (Netherlands)

    Helliwell, P.S.; Fitzgerald, O.; Fransen, J.

    2014-01-01

    OBJECTIVE: There are several new composite indices for assessing disease activity in psoriatic arthritis (PsA). Each may function as a disease state variable and a responder index. The aim of our study was to determine cutoffs for disease activity and response. METHODS: Data from the Group for GRAPP

  11. 34 CFR 363.4 - What are the authorized activities under a State Supported Employment Services grant?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false What are the authorized activities under a State Supported Employment Services grant? 363.4 Section 363.4 Education Regulations of the Offices of the... EDUCATION THE STATE SUPPORTED EMPLOYMENT SERVICES PROGRAM General § 363.4 What are the authorized...

  12. 10 CFR 50.13 - Attacks and destructive acts by enemies of the United States; and defense activities.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Attacks and destructive acts by enemies of the United... destructive acts by enemies of the United States; and defense activities. An applicant for a license to... an enemy of the United States, whether a foreign government or other person, or (b) use or...

  13. 77 FR 64386 - Agency Information Collection Activities (Per Diem for Nursing Home Care of Veterans in State...

    Science.gov (United States)

    2012-10-19

    ... AFFAIRS Agency Information Collection Activities (Per Diem for Nursing Home Care of Veterans in State Homes; Per Diem for Adult Day Care of Veterans in State Homes) Under OMB Review AGENCY: Veterans Health... day health services care to Veterans. VA requires facilities providing nursing home and adult...

  14. Relationships between physical education students' motivational profiles, enjoyment, state anxiety, and self-reported physical activity.

    Science.gov (United States)

    Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo; Nurmi, Jari-Erik

    2009-01-01

    The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000) and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213) completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education. Key pointsTWO MOTIVATIONAL PROFILES WERE REVEALED: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation.The students in the first profile enjoyed physical education more and were physically more active than the students in the second profile.Moreover, the representatives of the "High motivation profile "experienced greater anxiety toward physical education than the representatives of the "Low motivation profile"These findings raised an interesting question whether students engaging in physical education benefit more from the presence of both self-determined and non-self-determined forms of motivation, or are the benefits higher if students are primarily self-determined?

  15. Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

    Science.gov (United States)

    Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

    2015-01-22

    Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition.

  16. Single-unit activity in piriform cortex during slow-wave state is shaped by recent odor experience.

    Science.gov (United States)

    Wilson, Donald A

    2010-02-03

    Memory and its underlying neural plasticity play important roles in sensory discrimination and cortical pattern recognition in olfaction. Given the reported function of slow-wave sleep states in neocortical and hippocampal memory consolidation, we hypothesized that activity during slow-wave states within the piriform cortex may be shaped by recent olfactory experience. Rats were anesthetized with urethane and allowed to spontaneously shift between slow-wave and fast-wave states as recorded in local field potentials within the anterior piriform cortex. Single-unit activity of piriform cortical layer II/III neurons was recorded simultaneously. The results suggest that piriform cortical activity during slow-wave states is shaped by recent (several minutes) odor experience. The temporal structure of single-unit activity during slow waves was modified if the animal had been stimulated with an odor within the receptive field of that cell. If no odor had been delivered, the activity of the cell during slow-wave activity was stable across the two periods. The results demonstrate that piriform cortical activity during slow-wave state is shaped by recent odor experience, which could contribute to odor memory consolidation.

  17. Computational state space models for activity and intention recognition. A feasibility study.

    Directory of Open Access Journals (Sweden)

    Frank Krüger

    Full Text Available BACKGROUND: Computational state space models (CSSMs enable the knowledge-based construction of Bayesian filters for recognizing intentions and reconstructing activities of human protagonists in application domains such as smart environments, assisted living, or security. Computational, i. e., algorithmic, representations allow the construction of increasingly complex human behaviour models. However, the symbolic models used in CSSMs potentially suffer from combinatorial explosion, rendering inference intractable outside of the limited experimental settings investigated in present research. The objective of this study was to obtain data on the feasibility of CSSM-based inference in domains of realistic complexity. METHODS: A typical instrumental activity of daily living was used as a trial scenario. As primary sensor modality, wearable inertial measurement units were employed. The results achievable by CSSM methods were evaluated by comparison with those obtained from established training-based methods (hidden Markov models, HMMs using Wilcoxon signed rank tests. The influence of modeling factors on CSSM performance was analyzed via repeated measures analysis of variance. RESULTS: The symbolic domain model was found to have more than 10(8 states, exceeding the complexity of models considered in previous research by at least three orders of magnitude. Nevertheless, if factors and procedures governing the inference process were suitably chosen, CSSMs outperformed HMMs. Specifically, inference methods used in previous studies (particle filters were found to perform substantially inferior in comparison to a marginal filtering procedure. CONCLUSIONS: Our results suggest that the combinatorial explosion caused by rich CSSM models does not inevitably lead to intractable inference or inferior performance. This means that the potential benefits of CSSM models (knowledge-based model construction, model reusability, reduced need for training data are

  18. Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active lysine with γ-thialysine by using a chemical mutagenesis strategy.

    Science.gov (United States)

    Timms, Nicole; Windle, Claire L; Polyakova, Anna; Ault, James R; Trinh, Chi H; Pearson, Arwen R; Nelson, Adam; Berry, Alan

    2013-03-01

    Chemical modification has been used to introduce the unnatural amino acid γ-thialysine in place of the catalytically important Lys165 in the enzyme N-acetylneuraminic acid lyase (NAL). The Staphylococcus aureus nanA gene, encoding NAL, was cloned and expressed in E. coli. The protein, purified in high yield, has all the properties expected of a class I NAL. The S. aureus NAL which contains no natural cysteine residues was subjected to site-directed mutagenesis to introduce a cysteine in place of Lys165 in the enzyme active site. Subsequently chemical mutagenesis completely converted the cysteine into γ-thialysine through dehydroalanine (Dha) as demonstrated by ESI-MS. Initial kinetic characterisation showed that the protein containing γ-thialysine regained 17 % of the wild-type activity. To understand the reason for this lower activity, we solved X-ray crystal structures of the wild-type S. aureus NAL, both in the absence of, and in complex with, pyruvate. We also report the structures of the K165C variant, and the K165-γ-thialysine enzyme in the presence, or absence, of pyruvate. These structures reveal that γ-thialysine in NAL is an excellent structural mimic of lysine. Measurement of the pH-activity profile of the thialysine modified enzyme revealed that its pH optimum is shifted from 7.4 to 6.8. At its optimum pH, the thialysine-containing enzyme showed almost 30 % of the activity of the wild-type enzyme at its pH optimum. The lowered activity and altered pH profile of the unnatural amino acid-containing enzyme can be rationalised by imbalances of the ionisation states of residues within the active site when the pK(a) of the residue at position 165 is perturbed by replacement with γ-thialysine. The results reveal the utility of chemical mutagenesis for the modification of enzyme active sites and the exquisite sensitivity of catalysis to the local structural and electrostatic environment in NAL.

  19. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning

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    Miriam Shirin Nokia

    2012-12-01

    Full Text Available Oscillations in hippocampal local-field potentials reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz oscillations and ripples (~200 Hz occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs, hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval, when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

  20. Solid-State Synthesis and Photocatalytic Activity of Polyterthiophene Derivatives/TiO2 Nanocomposites

    Directory of Open Access Journals (Sweden)

    Ruxangul Jamal

    2014-05-01

    Full Text Available Poly(3,4-propylenedioxy-2,2':5',2"-terthiophene/TiO2 and poly(3,4-(2,2-dimethylenepropylenedioxy-2,2':5',2"-terthiophene/TiO2 nanocomposites were synthesized by a simple solid-state method. Additionally, the poly(3,4-propylenedioxy thiophene/TiO2 and poly(3,4-2,2-dimethylenepropylenedioxythiophene/TiO2 nanocomposites were synthesized in a similar manner for comparison. The structure and morphology were characterized by Fourier transform infrared (FTIR, ultraviolet-visible (UV-Vis absorption spectroscopy, X-ray diffraction (XRD and transmission electron microscopy (TEM. The photocatalytic activities of the nanocomposites were examined through the degradation processes of a methylene blue (MB solution under UV light and sunlight irradiation. The results of FTIR and UV-Vis spectra showed that the composites were successfully synthesized by solid-state method and the poly(3,4-propylenedioxy-2,2':5',2"-terthiophene/TiO2 and poly(3,4-(2,2-dimethylenepropylenedioxy-2,2':5',2"-terthiophene/TiO2 nanocomposite had a higher oxidation degree and conjugation length than others. The results also indicated that the TiO2 had no effect on the crystallinity of composites, but was well embedded in the polymer matrix. Additionally, the highest degradation efficiency of 90.5% occurred in the case of the poly(3,4-propylenedioxy-2,2':5',2"-terthiophene/TiO2 nanocomposite.