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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. Activating Welfare States

    DEFF Research Database (Denmark)

    Kvist, Jon

    This paper investigates how welfare states may actively contribute to promote employment opportunities, i.e. participation in the labour market through various operations and policies. The principal operations concern in particular the de-familiarisation of caring tasks through social services...

  4. Neural activity when people solve verbal problems with insight.

    Directory of Open Access Journals (Sweden)

    Mark Jung-Beeman

    2004-04-01

    Full Text Available People sometimes solve problems with a unique process called insight, accompanied by an "Aha!" experience. It has long been unclear whether different cognitive and neural processes lead to insight versus noninsight solutions, or if solutions differ only in subsequent subjective feeling. Recent behavioral studies indicate distinct patterns of performance and suggest differential hemispheric involvement for insight and noninsight solutions. Subjects solved verbal problems, and after each correct solution indicated whether they solved with or without insight. We observed two objective neural correlates of insight. Functional magnetic resonance imaging (Experiment 1 revealed increased activity in the right hemisphere anterior superior temporal gyrus for insight relative to noninsight solutions. The same region was active during initial solving efforts. Scalp electroencephalogram recordings (Experiment 2 revealed a sudden burst of high-frequency (gamma-band neural activity in the same area beginning 0.3 s prior to insight solutions. This right anterior temporal area is associated with making connections across distantly related information during comprehension. Although all problem solving relies on a largely shared cortical network, the sudden flash of insight occurs when solvers engage distinct neural and cognitive processes that allow them to see connections that previously eluded them.

  5. Insight into Nek2A activity regulation and its pharmacological ...

    African Journals Online (AJOL)

    Ambuj Kumar

    2012-11-28

    Nov 28, 2012 ... 3. Nek2A activity regulation and associated pathological outcomes . .... vide a detailed insight into how they coordinate the cell cycle .... the adenine subpocket creating steric hindrance in the plane of ... Three dimensional.

  6. 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

  7. 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 ...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. 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.

  16. X-ray-induced catalytic active-site reduction of a multicopper oxidase: structural insights into the proton-relay mechanism and O2 -reduction states

    Energy Technology Data Exchange (ETDEWEB)

    Serrano-Posada, Hugo; Centeno-Leija, Sara; Rojas-Trejo, Sonia Patricia; Rodríguez-Almazán, Claudia; Stojanoff, Vivian; Rudiño-Piñera, Enrique

    2015-11-26

    During X-ray data collection from a multicopper oxidase (MCO) crystal, electrons and protons are mainly released into the system by the radiolysis of water molecules, leading to the X-ray-induced reduction of O2 to 2H2O at the trinuclear copper cluster (TNC) of the enzyme. In this work, 12 crystallographic structures of Thermus thermophilus HB27 multicopper oxidase (Tth-MCO) in holo, apo and Hg-bound forms and with different X-ray absorbed doses have been determined. In holo Tth -MCO structures with four Cu atoms, the proton-donor residue Glu451 involved in O2 reduction was found in a double conformation: Glu451a (~7 Å from the TNC) and Glu451b (~4.5 Å from the TNC). A positive peak of electron density above 3.5σ in anFo-Fc map for Glu451a Oε2 indicates the presence of a carboxyl functional group at the side chain, while its significant absence in Glu451b strongly suggests a carboxylate functional group. In contrast, for apo Tth -MCO and in Hg-bound structures neither the positive peak nor double conformations were observed. Together, these observations provide the first structural evidence for a proton-relay mechanism in the MCO family and also support previous studies indicating that Asp106 does not provide protons for this mechanism. In addition, eight composite structures (Tth -MCO-C1–8) with different X-ray-absorbed doses allowed the observation of different O2-reduction states, and a total depletion of T2Cu at doses higher than 0.2 MGy showed the high susceptibility of this Cu atom to radiation damage, highlighting the importance of taking radiation effects into account in biochemical interpretations of an MCO structure.

  17. 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.

  18. Frozen steady states in active systems

    CERN Document Server

    Schaller, Volker; Hammerich, Benjamin; Frey, Erwin; Bausch, Andreas R

    2011-01-01

    Even simple active systems can show a plethora of intriguing phenomena and often we find complexity were we would have expected simplicity. One striking example is the occurrence of a quiescent or absorbing state with frozen fluctuations that at first sight seems to be impossible for active matter driven by the incessant input of energy. While such states were reported for externally driven systems through macroscopic shear or agitation, the investigation of frozen active states in inherently active systems like cytoskeletal suspensions or active gels is still at large. Using high density motility assay experiments, we demonstrate that frozen steady states can arise in active systems if active transport is coupled to growth processes. The experiments are complemented by agent-based simulations which identify the coupling between self-organization, growth and mechanical properties to be responsible for the pattern formation process.

  19. 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...

  20. 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

  1. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase.

    Science.gov (United States)

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J; Davies, Gareth; Holdgate, Geoffrey A; Phillips, Chris; Tucker, Julie A; Norman, Richard A; Scott, Andrew D; Higazi, Daniel R; Lowe, David; Thompson, Gary S; Breeze, Alexander L

    2015-07-23

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called 'DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a 'DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and 'molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1.

  2. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase

    Science.gov (United States)

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J.; Davies, Gareth; Holdgate, Geoffrey A.; Phillips, Chris; Tucker, Julie A.; Norman, Richard A.; Scott, Andrew D.; Higazi, Daniel R.; Lowe, David; Thompson, Gary S.; Breeze, Alexander L.

    2015-01-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called ‘DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a ‘DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and ‘molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1. PMID:26203596

  3. 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.

  4. 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.

  5. Diversity of Active States in TMT Opsins.

    Directory of Open Access Journals (Sweden)

    Kazumi Sakai

    Full Text Available Opn3/TMT opsins belong to one of the opsin groups with vertebrate visual and non-visual opsins, and are widely distributed in eyes, brains and other internal organs in various vertebrates and invertebrates. Vertebrate Opn3/TMT opsins are further classified into four groups on the basis of their amino acid identities. However, there is limited information about molecular properties of these groups, due to the difficulty in preparing the recombinant proteins. Here, we successfully expressed recombinant proteins of TMT1 and TMT2 opsins of medaka fish (Oryzias latipes in cultured cells and characterized their molecular properties. Spectroscopic and biochemical studies demonstrated that TMT1 and TMT2 opsins functioned as blue light-sensitive Gi/Go-coupled receptors, but exhibited spectral properties and photo-convertibility of the active state different from each other. TMT1 opsin forms a visible light-absorbing active state containing all-trans-retinal, which can be photo-converted to 7-cis- and 9-cis-retinal states in addition to the original 11-cis-retinal state. In contrast, the active state of TMT2 opsin is a UV light-absorbing state having all-trans-retinal and does not photo-convert to any other state, including the original 11-cis-retinal state. Thus, TMT opsins are diversified so as to form a different type of active state, which may be responsible for their different functions.

  6. 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.

  7. Metaproteomics Provides Functional Insight into Activated Sludge Wastewater Treatment

    Science.gov (United States)

    Wilmes, Paul; Wexler, Margaret; Bond, Philip L.

    2008-01-01

    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 α-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 β 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. PMID:18392150

  8. Physical activity, stress reduction, and mood: insight into immunological mechanisms.

    Science.gov (United States)

    Hamer, Mark; Endrighi, Romano; Poole, Lydia

    2012-01-01

    Psychosocial factors, such as chronic mental stress and mood, are recognized as an important predictor of longevity and wellbeing. In particular, depression is independently associated with cardiovascular disease and all-cause mortality, and is often comorbid with chronic diseases that can worsen their associated health outcomes. Regular exercise is thought to be associated with stress reduction and better mood, which may partly mediate associations between depression, stress, and health outcomes. The underlying mechanisms for the positive effects of exercise on wellbeing remain poorly understood. In this overview we examine epidemiological evidence for an association between physical activity and mental health. We then describe the exercise withdrawal paradigm as an experimental protocol to study mechanisms linking exercise, mood, and stress. In particular we will discuss the potential role of the inflammatory response as a central mechanism.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. The role of alpha-rhythm states in perceptual learning: insights from experiments and computational models

    Science.gov (United States)

    Sigala, Rodrigo; Haufe, Sebastian; Roy, Dipanjan; Dinse, Hubert R.; Ritter, Petra

    2014-01-01

    During the past two decades growing evidence indicates that brain oscillations in the alpha band (~10 Hz) not only reflect an “idle” state of cortical activity, but also take a more active role in the generation of complex cognitive functions. A recent study shows that more than 60% of the observed inter-subject variability in perceptual learning can be ascribed to ongoing alpha activity. This evidence indicates a significant role of alpha oscillations for perceptual learning and hence motivates to explore the potential underlying mechanisms. Hence, it is the purpose of this review to highlight existent evidence that ascribes intrinsic alpha oscillations a role in shaping our ability to learn. In the review, we disentangle the alpha rhythm into different neural signatures that control information processing within individual functional building blocks of perceptual learning. We further highlight computational studies that shed light on potential mechanisms regarding how alpha oscillations may modulate information transfer and connectivity changes relevant for learning. To enable testing of those model based hypotheses, we emphasize the need for multidisciplinary approaches combining assessment of behavior and multi-scale neuronal activity, active modulation of ongoing brain states and computational modeling to reveal the mathematical principles of the complex neuronal interactions. In particular we highlight the relevance of multi-scale modeling frameworks such as the one currently being developed by “The Virtual Brain” project. PMID:24772077

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Wind Lidar Activities in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, Andrew; Newman, Jennifer; St. Pe, Alexandra; Iungo, G. Valerio; Wharton, Sonia; Herges, Tommy; Filippelli, Matthew; Pontbriand, Philippe; Osler, Evan

    2017-06-28

    IEA Wind Task 32 seeks to identify and mitigate the barriers to the adoption of lidar for wind energy applications. This work is partly achieved by sharing experience across researchers and practitioners in the United States and worldwide. This presentation is a short summary of some wind lidar-related activities taking place in the country, and was presented by Andrew Clifton at the Task 32 meeting in December 2016 in his role as the U.S. Department of Energy-nominated country representative to the task.

  1. Structure of the cathelicidin motif of protegrin-3 precursor: structural insights into the activation mechanism of an antimicrobial protein.

    Science.gov (United States)

    Sanchez, Jean-Frédéric; Hoh, François; Strub, Marie-Paule; Aumelas, André; Dumas, Christian

    2002-10-01

    Cathelicidins are a family of antimicrobial proteins isolated from leucocytes and epithelia cells that contribute to the innate host defense mechanisms in mammalians. Located in the C-terminal part of the holoprotein, the cathelicidin-derived antimicrobial peptide is liberated by a specific protease cleavage. Here, we report the X-ray structure of the cathelicidin motif of protegrin-3 solved by MAD phasing using the selenocysteine-labeled protein. Its overall structure represents a fold homologous to the cystatin family and adopts two native states, a monomer, and a domain-swapped dimer. This crystal structure is the first example of a structural characterization of the highly conserved cathelicidin motif and thus provides insights into the possible mechanism of activation of the antimicrobial protegrin peptide.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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 ...

  7. An insight into the removal of fluoroquinolones in activated sludge process: Sorption and biodegradation characteristics.

    Science.gov (United States)

    Wang, Lu; Qiang, Zhimin; Li, Yangang; Ben, Weiwei

    2017-06-01

    The detailed sorption steps and biodegradation characteristics of fluoroquinolones (FQs) including ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and ofloxacin were investigated through batch experiments. The results indicate that FQs at a total concentration of 500μg/L caused little inhibition of sludge bioactivity. Sorption was the primary removal pathway of FQs in the activated sludge process, followed by biodegradation, while hydrolysis and volatilization were negligible. FQ sorption on activated sludge was a reversible process governed by surface reaction. Henry and Freundlich models could describe the FQ sorption isotherms well in the concentration range of 100-300μg/L. Thermodynamic parameters revealed that FQ sorption on activated sludge is spontaneous, exothermic, and enthalpy-driven. Hydrophobicity-independent mechanisms determined the FQ sorption affinity with activated sludge. The zwitterion of FQs had the strongest sorption affinity, followed by cation and anion, and aerobic condition facilitated FQ sorption. FQs were slowly biodegradable, with long half-lives (>100hr). FQ biodegradation was enhanced with increasing temperature and under aerobic condition, and thus was possibly achieved through co-metabolism during nitrification. This study provides an insight into the removal kinetics and mechanism of FQs in the activated sludge process, but also helps assess the environmental risks of FQs resulting from sludge disposal. Copyright © 2016. Published by Elsevier B.V.

  8. Physical activity counseling in primary care: Insights from public health and behavioral economics.

    Science.gov (United States)

    Shuval, Kerem; Leonard, Tammy; Drope, Jeffrey; Katz, David L; Patel, Alpa V; Maitin-Shepard, Melissa; Amir, On; Grinstein, Amir

    2017-05-06

    Physical inactivity has reached epidemic proportions in modern society. Abundant evidence points to a causal link between physical inactivity and increased risk for numerous noncommunicable diseases, such as some types of cancer and heart disease, as well as premature mortality. Yet, despite this overwhelming evidence, many individuals do not meet the recommended amount of physical activity required to achieve maximum health benefits. Because primary care physicians' advice is highly regarded, clinicians have the unique opportunity to play an important role in enabling patients to modify their behavior at the point of care with the goal of guiding patients to adopt and maintain an active lifestyle. In the current study, the authors evaluate pertinent literature from the fields of medicine/public health and economics/psychology to suggest a comprehensive approach to physical activity counseling at the primary care level. They first examine the public health approach to physical activity counseling, and then proceed to offer insights from behavioral economics, an emerging field that combines principles from psychology and economics. The application of key behavioral economics tools (eg, precommitment contracts, framing) to physical activity counseling in primary care is elaborated. CA Cancer J Clin 2017;67:233-244. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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

    2016-03-28

    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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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,…

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Stated Uptake of Physical Activity Rewards Programmes Among Active and Insufficiently Active Full-Time Employees.

    Science.gov (United States)

    Ozdemir, Semra; Bilger, Marcel; Finkelstein, Eric A

    2017-04-22

    Employers are increasingly relying on rewards programmes in an effort to promote greater levels of activity among employees; however, if enrolment in these programmes is dominated by active employees, then they are unlikely to be a good use of resources. This study uses a stated-preference survey to better understand who participates in rewards-based physical activity programmes, and to quantify stated uptake by active and insufficiently active employees. The survey was fielded to a national sample of 950 full-time employees in Singapore between 2012 and 2013. Participants were asked to choose between hypothetical rewards programmes that varied along key dimensions and whether or not they would join their preferred programme if given the opportunity. A mixed logit model was used to analyse the data and estimate predicted uptake for specific programmes. We then simulated employer payments based on predictions for the percentage of each type of employee likely to meet the activity goal. Stated uptake ranged from 31 to 67% of employees, depending on programme features. For each programme, approximately two-thirds of those likely to enrol were insufficiently active. Results showed that insufficiently active employees, who represent the majority, are attracted to rewards-based physical activity programmes, and at approximately the same rate as active employees, even when enrolment fees are required. This suggests that a programme with generous rewards and a modest enrolment fee may have strong employee support and be within the range of what employers may be willing to spend.

  6. Structural insights for activation of retinal guanylate cyclase by GCAP1.

    Directory of Open Access Journals (Sweden)

    Sunghyuk Lim

    Full Text Available Guanylyl cyclase activating protein 1 (GCAP1, a member of the neuronal calcium sensor (NCS subclass of the calmodulin superfamily, confers Ca(2+-sensitive activation of retinal guanylyl cyclase 1 (RetGC1 upon light activation of photoreceptor cells. Here we present NMR assignments and functional analysis to probe Ca(2+-dependent structural changes in GCAP1 that control activation of RetGC. NMR assignments were obtained for both the Ca(2+-saturated inhibitory state of GCAP1 versus a GCAP1 mutant (D144N/D148G, called EF4mut, which lacks Ca(2+ binding in EF-hand 4 and models the Ca(2+-free/Mg(2+-bound activator state of GCAP1. NMR chemical shifts of backbone resonances for Ca(2+-saturated wild type GCAP1 are overall similar to those of EF4mut, suggesting a similar main chain structure for assigned residues in both the Ca(2+-free activator and Ca(2+-bound inhibitor states. This contrasts with large Ca(2+-induced chemical shift differences and hence dramatic structural changes seen for other NCS proteins including recoverin and NCS-1. The largest chemical shift differences between GCAP1 and EF4mut are seen for residues in EF4 (S141, K142, V145, N146, G147, G149, E150, L153, E154, M157, E158, Q161, L166, but mutagenesis of EF4 residues (F140A, K142D, L153R, L166R had little effect on RetGC1 activation. A few GCAP1 residues in EF-hand 1 (K23, T27, G32 also show large chemical shift differences, and two of the mutations (K23D and G32N each decrease the activation of RetGC, consistent with a functional conformational change in EF1. GCAP1 residues at the domain interface (V77, A78, L82 have NMR resonances that are exchange broadened, suggesting these residues may be conformationally dynamic, consistent with previous studies showing these residues are in a region essential for activating RetGC1.

  7. 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.

  8. 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…

  9. 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.

  10. 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.

  11. 'Maximising shareholder value': a detailed insight into the corporate political activity of the Australian food industry.

    Science.gov (United States)

    Mialon, Melissa; Swinburn, Boyd; Allender, Steven; Sacks, Gary

    2017-04-01

    To gain deeper insight into the corporate political activity (CPA) of the Australian food industry from a public health perspective. Fifteen interviews with a purposive sample of current and former policy makers, public health advocates and academics who have closely interacted with food industry representatives or observed food industry behaviours. All participants reported having directly experienced the CPA of the food industry during their careers, with the 'information and messaging' and 'constituency building' strategies most prominent. Participants expressed concern that food industry CPA strategies resulted in weakened policy responses to addressing diet-related disease. This study provides direct evidence of food industry practices that have the potential to shape public health-related policies and programs in Australia in ways that favour business interests at the expense of population health. Implications for public health: This evidence can inform policy makers and public health advocates and be used to adopt measures to ensure that public interests are put at the forefront as part of the policy development and implementation process. © 2017 The Authors.

  12. 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

  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. 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

  15. 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

  16. 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.

  17. 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.

  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. 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.

  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. 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.

  2. Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR

    Science.gov (United States)

    Hong, Mei; Su, Yongchao

    2011-01-01

    Many membrane peptides and protein domains contain functionally important cationic Arg and Lys residues, whose insertion into the hydrophobic interior of the lipid bilayer encounters significant energy barriers. To understand how these cationic molecules overcome the free energy barrier to insert into the lipid membrane, we have used solid-state NMR spectroscopy to determine the membrane-bound topology of these peptides. A versatile array of solid-state NMR experiments now readily yields the conformation, dynamics, orientation, depth of insertion, and site-specific protein–lipid interactions of these molecules. We summarize key findings of several Arg-rich membrane peptides, including β-sheet antimicrobial peptides, unstructured cell-penetrating peptides, and the voltage-sensing helix of voltage-gated potassium channels. Our results indicate the central role of guanidinium-phosphate and guanidinium-water interactions in dictating the structural topology of these cationic molecules in the lipid membrane, which in turn account for the mechanisms of this functionally diverse class of membrane peptides. PMID:21344534

  3. 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...

  4. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase

    OpenAIRE

    Klein, T.; Vajpai, N; Phillips, JJ; Davies, G; Holdgate, GA; Phillips, C.; Tucker, JA; Norman, RA; Scott, AD; Higazi, DR; Lowe, D; Thompson, GS; Breeze, A

    2015-01-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called ‘DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a ‘DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the ...

  5. 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.

  6. Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic

    Science.gov (United States)

    Perry, Kay; Hwang, Young; Bushman, Frederic D.; Van Duyne, Gregory D.

    2010-01-01

    Summary Poxviruses encode their own type IB topoisomerases (TopIBs) which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves a novel Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small vs. large enzyme subfamilies. PMID:20152159

  7. 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.

  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. 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.

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

    Science.gov (United States)

    Newhall, Katherine A.; Vanden-Eijnden, Eric

    2017-06-01

    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 x\\in [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

  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. Atomic substitutions in synthetic apatite; Insights from solid-state NMR spectroscopy

    Science.gov (United States)

    Vaughn, John S.

    Apatite, Ca5(PO4)3X (where X = F, Cl, or OH), is a unique mineral group capable of atomic substitutions for cations and anions of varied size and charge. Accommodation of differing substituents requires some kind of structural adaptation, e.g. new atomic positions, vacancies, or coupled substitutions. These structural adaptations often give rise to important physicochemical properties relevant to a range of scientific disciplines. Examples include volatile trapping during apatite crystallization, substitution for large radionuclides for long-term storage of nuclear fission waste, substitution for fluoride to improve acid resistivity in dental enamel composed dominantly of hydroxylapatite, and the development of novel biomaterials with enhanced biocompatibility. Despite the importance and ubiquity of atomic substitutions in apatite materials, many of the mechanisms by which these reactions occur are poorly understood. Presence of substituents at dilute concentration and occupancy of disordered atomic positions hinder detection by bulk characterization methods such as X-ray diffraction (XRD) and infrared (IR) spectroscopy. Solid-state nuclear magnetic resonance (NMR) spectroscopy is an isotope-specific structural characterization technique that does not require ordered atomic arrangements, and is therefore well suited to investigate atomic substitutions and structural adaptations in apatite. In the present work, solid-state NMR is utilized to investigate structural adaptations in three different types of apatite materials; a series of near-binary F, Cl apatite, carbonate-hydroxylapatite compositions prepared under various synthesis conditions, and a heat-treated hydroxylapatite enriched in 17O. The results indicate that hydroxyl groups in low-H, near binary F,Cl apatite facilitate solid-solution between F and Cl via column reversals, which result in average hexagonal symmetry despite very dilute OH concentration ( 2 mol percent). In addition, 19F NMR spectra indicate

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Electrospray ionization ion mobility mass spectrometry provides novel insights into the pattern and activity of fetal hippocampus gangliosides.

    Science.gov (United States)

    Sarbu, Mirela; Vukelić, Željka; Clemmer, David E; Zamfir, Alina D

    2017-08-01

    Gangliosides (GGs), a particular class of glycosphingolipids ubiquitously found in tissues and body fluids, exhibit the highest expression in the central nervous system, especially in brain. GGs are involved in crucial processes, such as neurogenesis, synaptogenesis, synaptic transmission, cell adhesion, growth and proliferation. For these reasons, efforts are constantly invested into development and refinement of specific methods for GG analysis. We have recently shown that ion mobility separation (IMS) mass spectrometry (MS) has the capability to provide consistent compositional and structural information on GGs at high sensitivity, resolution and mass accuracy. In the present paper, we have implemented IMS MS for the first time in the study of a highly complex native GG mixture extracted and purified from human fetal hippocampus. As compared to previous studies, where no separation techniques prior to MS were applied, IMS MS technique has not just generated valuable novel information on the GG pattern characteristic for hippocampus in early developmental stage, but also provided data related to the GG molecular involvement in the synaptic functions by the discovery of 25 novel structures modified by CH3COO(-). The detection and identification in fetal hippocampus of a much larger number of GG species than ever reported before was possible due to the ion mobility separation according to the charge state, the carbohydrate chain length and the degree of sialylation. By applying IMS in conjunction with collision induced dissociation (CID) tandem MS (MS/MS), novel GG species modified by CH3COO(-) attachment, discovered here for the first time, were sequenced and structurally investigated in details. The present findings, based on IMS MS, provide a more reliable insight into the expression and role of gangliosides in human hippocampus, with a particular emphasis on their cholinergic activity at this level. Copyright © 2017 Elsevier B.V. and Société Française de

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Disrupted relationship between "resting state" connectivity and task-evoked activity during social perception in schizophrenia.

    Science.gov (United States)

    Ebisch, Sjoerd J H; Gallese, Vittorio; Salone, Anatolia; Martinotti, Giovanni; di Iorio, Giuseppe; Mantini, Dante; Perrucci, Mauro Gianni; Romani, Gian Luca; Di Giannantonio, Massimo; Northoff, Georg

    2017-07-20

    Schizophrenia has been described as a self-disorder, whereas social deficits are key features of the illness. Changes in "resting state" activity of brain networks involved in self-related processing have been consistently reported in schizophrenia, but their meaning for social perception deficits remains poorly understood. Here, we applied a novel approach investigating the relationship between task-evoked neural activity during social perception and functional organization of self-related brain networks during a "resting state". "Resting state" functional MRI was combined with task-related functional MRI using a social perception experiment. Twenty-one healthy control participants (HC) and 21 out-patients with a diagnosis of schizophrenia (SCH) were included. There were no significant differences concerning age, IQ, education and gender between the groups. Results showed reduced "resting state" functional connectivity between ventromedial prefrontal cortex and dorsal posterior cingulate cortex in SCH, compared to HC. During social perception, neural activity in dorsal posterior cingulate cortex and behavioral data indicated impaired congruence coding of social stimuli in SCH. Task-evoked activity during social perception in dorsal posterior cingulate cortex co-varied with dorsal posterior cingulate cortex-ventromedial prefrontal cortex functional connectivity during a "resting state" in HC, but not in SCH. Task-evoked activity also correlated with negative symptoms in SCH. These preliminary findings, showing disrupted prediction of social perception measures by "resting state" functioning of self-related brain networks in schizophrenia, provide important insight in the hypothesized link between self and social deficits. They also shed light on the meaning of "resting state" changes for tasks such as social perception. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 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…

  8. 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...

  9. Physical activity in Georgia state parks: A pilot study

    Science.gov (United States)

    Lincoln R. Larson; Jason W. Whiting; Gary T. Green

    2012-01-01

    This pilot study assessed the role of Georgia State Parks in the promotion of physical activity among different racial/ethnic and age groups. Data were collected at three state parks in north Georgia during the summer of 2009 using two research methods: behavior observations (N=2281) and intercept surveys (N=473).

  10. 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.

  11. 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.

  12. Strategic Priorities for Physical Activity Surveillance in the United States.

    Science.gov (United States)

    Fulton, Janet E; Carlson, Susan A; Ainsworth, Barbara E; Berrigan, David; Carlson, Cynthia; Dorn, Joan M; Heath, Gregory W; Kohl, Harold W; Lee, I-Min; Lee, Sarah M; Másse, Louise C; Morrow, James R; Gabriel, Kelley Pettee; Pivarnik, James M; Pronk, Nicolaas P; Rodgers, Anne B; Saelens, Brian E; Sallis, James F; Troiano, Richard P; Tudor-Locke, Catrine; Wendel, Arthur

    2016-10-01

    Develop strategic priorities to guide future physical activity surveillance in the United States. The Centers for Disease Control and Prevention and the American College of Sports Medicine convened a scientific roundtable of physical activity and measurement experts. Participants summarized the current state of aerobic physical activity surveillance for adults, focusing on practice and research needs in three areas: 1) behavior, 2) human movement, and 3) community supports. Needs and challenges for each area were identified. At the conclusion of the meeting, experts identified one overarching strategy and five strategic priorities to guide future surveillance. The identified overarching strategy was to develop a national plan for physical activity surveillance similar to the U.S. National Physical Activity Plan for promotion. The purpose of the plan would be to enhance coordination and collaboration within and between sectors, such as transportation and public health, and to address specific strategic priorities identified at the roundtable. These strategic priorities were used 1) to identify and prioritize physical activity constructs; 2) to assess the psychometric properties of instruments for physical activity surveillance; 3) to provide training and technical assistance for those collecting, analyzing, or interpreting surveillance data; 4) to explore accessing data from alternative sources; and 5) to improve communication, translation, and dissemination about estimates of physical activity from surveillance systems. This roundtable provided strategic priorities for physical activity surveillance in the United States. A first step is to develop a national plan for physical activity surveillance that would provide an operating framework from which to execute these priorities.

  13. 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)

  14. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Science.gov (United States)

    Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O’Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

    2017-01-01

    Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. PMID:28053511

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Resting-state functional connectivity between right anterior insula and right orbital frontal cortex correlate with insight level in obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Jie Fan

    2017-01-01

    Full Text Available Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD, though the salience network (SN has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs functional connectivity (FC of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI data from 21 OCD patients with good insight (OCD-GI, 19 OCD patients with poor insight (OCD-PI, and 24 healthy controls (HCs. Seed-based whole-brain FC and ROI (region of interest-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI and dorsal anterior cingulate cortex (dACC. The right AI-right medial orbital frontal cortex (mOFC connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI > OCD-PI > HC. Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes.

  1. 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.

  2. 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.

  3. 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.

  4. Maintenance and decline of physical activity during adolescence: insights from a qualitative study

    Directory of Open Access Journals (Sweden)

    Filion Annie

    2011-10-01

    Full Text Available Abstract Purpose Better knowledge on why some individuals succeed in maintaining participation in physical activity throughout adolescence is needed to guide the development of effective interventions to increase and then maintain physical activity levels. Despite allowing an in-depth understanding, qualitative designs have infrequently been used to study physical activity maintenance. We explored factors contributing to the maintenance and the decline of physical activity during adolescence. Methods Questionnaires were administered to 515 grade 10-12 students. The Physical Activity Questionnaire for Adolescents was used to determine physical activity level at the end of adolescence. An adapted version of this questionnaire was used to estimate physical activity in early adolescence. Among both genders, we identified participants who maintained a high level of physical activity since grade 7 and some whose activity level declined. For each category, groups of 10 students were randomly selected to take part in focus group discussions. Results Seven focus groups with 5 to 8 participants in each were held. Both maintainers and decliners associated physical activity with positive health outcomes. Maintenance of physical activity was associated with supportive social environments and heightened feelings of competence and attractiveness. A decline in physical activity was associated with negative social validation, poor social support and barriers related to access. Conclusions Although maintainers and decliners associate physical activity with similar themes, the experiences of both groups differ substantially with regards to those themes. Taking both perspectives in consideration could help improve interventions to increase and maintain physical activity levels of adolescents.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Directory of Open Access Journals (Sweden)

    Tintoré M

    2016-12-01

    Full Text Available Mar Tintoré,1 Maggie Alexander,2 Kathleen Costello,3 Martin Duddy,4 David E Jones,5 Nancy Law,6 Gilmore O’Neill,7 Antonio Uccelli,8 Robert Weissert,9 Sibyl Wray10 1Multiple Sclerosis Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain; 2European Multiple Sclerosis Platform, Brussels, Belgium; 3National Multiple Sclerosis Society, Denver, CO, USA; 4Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 5Department of Neurology, University of Virginia, Charlottesville, VA, USA; 6Nancy Law Consulting LLC, Parker, CO, USA; 7Biogen, Cambridge, MA, USA; 8Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 9Department of Neurology, University of Regensburg, Regensburg, Germany; 10Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA Background: Managing multiple sclerosis (MS treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods: A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results: A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT; satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment

  10. 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

  11. High Frequency State-Variable Biquadratic Active Filters

    Directory of Open Access Journals (Sweden)

    T. Dostal

    1998-04-01

    Full Text Available The state-variable (KHN active RC biquadratic filters with good performance in high frequency range , flexibility of outputs (LP, HP, BP, low sensitivities in novel current and hybrid modes, using current conveyors, transimpedance, trans-admittance and current operational amplifiers, are given in this paper.

  12. 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...

  13. 34 CFR 300.704 - State-level activities.

    Science.gov (United States)

    2010-07-01

    ... certify to the Secretary that the arrangements to establish responsibility for services pursuant to... transition of students with disabilities to postsecondary activities; (vii) To assist LEAs in meeting... State Medicaid program under Title XIX of the Social Security Act. (9) Funds reserved under paragraph...

  14. 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…

  15. 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.

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. Nonequilibrium Equation of State in Suspensions of Active Colloids

    Science.gov (United States)

    Ginot, Félix; Theurkauff, Isaac; Levis, Demian; Ybert, Christophe; Bocquet, Lydéric; Berthier, Ludovic; Cottin-Bizonne, Cécile

    2015-01-01

    Active colloids constitute a novel class of materials composed of colloidal-scale particles locally converting chemical energy into motility, mimicking micro-organisms. Evolving far from equilibrium, these systems display structural organizations and dynamical properties distinct from thermalized colloidal assemblies. Harvesting the potential of this new class of systems requires the development of a conceptual framework to describe these intrinsically nonequilibrium systems. We use sedimentation experiments to probe the nonequilibrium equation of state of a bidimensional assembly of active Janus microspheres and conduct computer simulations of a model of self-propelled hard disks. Self-propulsion profoundly affects the equation of state, but these changes can be rationalized using equilibrium concepts. We show that active colloids behave, in the dilute limit, as an ideal gas with an activity-dependent effective temperature. At finite density, increasing the activity is similar to increasing adhesion between equilibrium particles. We quantify this effective adhesion and obtain a unique scaling law relating activity and effective adhesion in both experiments and simulations. Our results provide a new and efficient way to understand the emergence of novel phases of matter in active colloidal suspensions.

  1. Nonequilibrium Equation of State in Suspensions of Active Colloids

    Directory of Open Access Journals (Sweden)

    Félix Ginot

    2015-01-01

    Full Text Available Active colloids constitute a novel class of materials composed of colloidal-scale particles locally converting chemical energy into motility, mimicking micro-organisms. Evolving far from equilibrium, these systems display structural organizations and dynamical properties distinct from thermalized colloidal assemblies. Harvesting the potential of this new class of systems requires the development of a conceptual framework to describe these intrinsically nonequilibrium systems. We use sedimentation experiments to probe the nonequilibrium equation of state of a bidimensional assembly of active Janus microspheres and conduct computer simulations of a model of self-propelled hard disks. Self-propulsion profoundly affects the equation of state, but these changes can be rationalized using equilibrium concepts. We show that active colloids behave, in the dilute limit, as an ideal gas with an activity-dependent effective temperature. At finite density, increasing the activity is similar to increasing adhesion between equilibrium particles. We quantify this effective adhesion and obtain a unique scaling law relating activity and effective adhesion in both experiments and simulations. Our results provide a new and efficient way to understand the emergence of novel phases of matter in active colloidal suspensions.

  2. 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.

  3. 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…

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. [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...

  11. 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...

  12. 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.

  13. Education Alignment and Accountability in an Era of Convergence: Policy Insights from States with Individual Learning Plans and Policies

    Science.gov (United States)

    Phelps, L. Allen; Durham, Julie; Wills, Joan

    2011-01-01

    In response to the rising demand for market-responsive education reform across the U.S., since 1998 more than twenty states have created Individual Learning or Graduation Plan (ILP/IGP) state policies. Using extensive policy document analyses and stakeholder interview data from four early-adopting ILP/IGP states, the goal of this four-state case…

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Annual and seasonal tornado activity in the United States and the global wind oscillation

    Science.gov (United States)

    Moore, Todd W.

    2017-08-01

    Previous studies have searched for relationships between tornado activity and atmospheric teleconnections to provide insight on the relationship between tornadoes, their environments, and larger scale patterns in the climate system. Knowledge of these relationships is practical because it can improve seasonal and sub-seasonal predictions of tornado probability and, therefore, help mitigate tornado-related losses. This study explores the relationships between the annual and seasonal tornado activity in the United States and the Global Wind Oscillation. Time series herein show that phases of the Global Wind Oscillation, and atmospheric angular momentum anomalies, vary over a period of roughly 20-25 years. Rank correlations indicate that tornado activity is weakly correlated with phases 2, 3, and 4 (positive) and 6, 7, and 8 (negative) of the Global Wind Oscillation in winter, spring, and fall. The correlation is not as clear in summer or at the annual scale. Non-parametric Mann-Whitney U tests indicate that winters and springs with more phase 2, 3, and 4 and fewer phase 6, 7, and 8 days tend to have more tornadoes. Lastly, logistic regression models indicate that winters and springs with more phase 2, 3, and 4 days have greater likelihoods of having more than normal tornado activity. Combined, these analyses suggest that seasons with more low atmospheric angular momentum days, or phase 2, 3, and 4 days, tend to have greater tornado activity than those with fewer days, and that this relationship is most evident in winter and spring.

  19. 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.

  20. 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.

  1. 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...

  2. Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity.

    Science.gov (United States)

    Tropak, Michael B; Zhang, Jianmin; Yonekawa, Sayuri; Rigat, Brigitte A; Aulakh, Virender S; Smith, Matthew R; Hwang, Hee-Jong; Ciufolini, Marco A; Mahuran, Don J

    2015-06-11

    In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward β-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 μM, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

  3. 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.

  4. 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.

  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. New insights into co-digestion of activated sludge and food waste: Biogas versus biofertilizer.

    Science.gov (United States)

    Ma, Yingqun; Yin, Yao; Liu, Yu

    2017-10-01

    This study explored two holistic approaches for co-digestion of activated sludge and food waste. In Approach 1, mixed activated sludge and food waste were first hydrolyzed with fungal mash, and produced hydrolysate without separation was directly subject to anaerobic digestion. In Approach 2, solid generated after hydrolysis of food waste by fungal mash was directly converted to biofertilizer, while separated liquid with high soluble COD concentration was further co-digested with activated sludge for biomethane production. Although the potential energy produced from Approach 1 was about 1.8-time higher than that from Approach 2, the total economic revenue generated from Approach 2 was about 1.9-fold of that from Approach 1 due to high market value of biofertilizer. It is expected that this study may lead to a paradigm shift in biosolid management towards environmental and economic sustainability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Activated and deactivated functional brain areas in the Deqi state

    Science.gov (United States)

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    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. PMID:25538761

  9. Activated and deactivated functional brain areas in the Deqi state

    OpenAIRE

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    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, th...

  10. 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

  11. A structural insight into lead neurotoxicity and calmodulin activation by heavy metals

    Science.gov (United States)

    Kursula, Petri; Majava, Viivi

    2007-01-01

    Calmodulin is a calcium sensor that is also capable of binding and being activated by other metal ions. Of specific interest in this respect is lead, which is known to be neurotoxic and to have a very high affinity towards calmodulin. Crystal structures of human calmodulin complexed with lead and barium ions have been solved. The results will help in understanding the activation mechanisms of calmodulin by different heavy metals and will provide a detailed view of a putative target for lead neurotoxicity in humans. PMID:17671360

  12. Integrin activation states and eosinophil recruitment in asthma

    Directory of Open Access Journals (Sweden)

    Mats W Johansson

    2013-04-01

    Full Text Available Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express α4β1, α6β1, αLβ2, αMβ2, αXβ2, αDβ2, and α4β7 integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs. Studies in mice indicate that both β1 and β2 integrins mediate eosinophil recruitment to the lung. In vitro studies indicate that α4β1 and αMβ2 are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 (VCAM-1 and the novel αMβ2 ligand periostin. In vivo, blood eosinophils have intermediate-activity β1 integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their β2 integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5. Airway eosinophils recovered by bronchoalveolar lavage (BAL after segmental antigen challenge have high-activity β1 integrins and high-activity αMβ2 that does not require IL-5. Here we review information on how the activation states of eosinophil β1 and β2 integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity α4β1 and αMβ2 of blood eosinophils are important for eosinophil arrest and consequently for recruitment and

  13. 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 group showed higher absolute power on the gamma band than did the control group (estimate = 0.434, 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 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

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. [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.

  1. 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

  2. Moving Souls: History Offers Insights into Physical Activity that Go beyond Fitness and Fun

    Science.gov (United States)

    Sydnor, Synthia

    2005-01-01

    This article looks at four theoretical themes that scholars insist on when studying history. The themes--social memory, liminality, community, and critique--may be useful in stimulating the direction, planning, and practice of physical activity in young adults. These particular themes were chosen because they seem to match some of the…

  3. 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

  4. Insights into cholinesterase inhibitory and antioxidant activities of five Juniperus species.

    Science.gov (United States)

    Orhan, Nilufer; Orhan, Ilkay Erdogan; Ergun, Fatma

    2011-09-01

    In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory and antioxidant activities of the aqueous and ethanol extracts of the leaves, ripe fruits, and unripe fruits of Juniperus communis ssp. nana, Juniperus oxycedrus ssp. oxycedrus, Juniperus sabina, Juniperus foetidissima, and Juniperus excelsa were investigated in the present study. Cholinesterase inhibition of the extracts was screened using ELISA microplate reader. Antioxidant activity of the extracts was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging, ferrous ion-chelating, and ferric-reducing antioxidant power (FRAP) assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The extracts had low or no inhibition towards AChE, whereas the leaf aqueous extract of J. foetidissima showed the highest BChE inhibition (93.94 ± 0.01%). The leaf extracts usually exerted higher antioxidant activity. We herein describe the first study on anticholinesterase and antioxidant activity by the methods of ferrous ion-chelating, superoxide radical scavenging, and ferric-reducing antioxidant power (FRAP) assays of the mentioned Juniperus species. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. 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

  6. 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.

  7. 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

  8. THE DISCOVERY OF THE FIRST “CHANGING LOOK” QUASAR: NEW INSIGHTS INTO THE PHYSICS AND PHENOMENOLOGY OF ACTIVE GALACTIC NUCLEI

    Energy Technology Data Exchange (ETDEWEB)

    LaMassa, Stephanie M.; Cales, Sabrina; Urry, C. Megan [Yale Center for Astronomy and Astrophysics, Physics Department, P.O. Box 208120, New Haven, CT 06520 (United States); Moran, Edward C. [Astronomy Department, Wesleyan University, Middletown, CT 06459 (United States); Myers, Adam D. [Department of Physics and Astronomy 3905, University of Wyoming, 1000 E. University, Laramaie, WY 82071 (United States); Richards, Gordon T. [Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Eracleous, Michael [Department of Astronomy and Astrophysics, and Institute for Gravitation and the Cosmos, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Heckman, Timothy M. [Department of Physics and Astronomy, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Gallo, Luigi [Department of Astronomy and Physics, Saint Mary’s University, Halifax, NS B3H 3C3 (Canada)

    2015-02-20

    SDSS J015957.64+003310.5 is an X-ray selected, z = 0.31 active galactic nucleus (AGN) from the Stripe 82X survey that transitioned from a Type 1 quasar to a Type 1.9 AGN between 2000 and 2010. This is the most distant AGN, and first quasar, yet observed to have undergone such a dramatic change. We re-observed the source with the double spectrograph on the Palomar 5 m telescope in 2014 July and found that the spectrum is unchanged since 2010. From fitting the optical spectra, we find that the AGN flux dropped by a factor of 6 between 2000 and 2010 while the broad Hα emission faded and broadened. Serendipitous X-ray observations caught the source in both the bright and dim state, showing a similar 2–10 keV flux diminution as the optical while lacking signatures of obscuration. The optical and X-ray changes coincide with g-band magnitude variations over multiple epochs of Stripe 82 observations. We demonstrate that variable absorption, as might be expected from the simplest AGN unification paradigm, does not explain the observed photometric or spectral properties. We interpret the changing state of J0159+0033 to be caused by dimming of the AGN continuum, reducing the supply of ionizing photons available to excite gas in the immediate vicinity around the black hole. J0159+0033 provides insight into the intermittency of black hole growth in quasars, as well as an unprecedented opportunity to study quasar physics (in the bright state) and the host galaxy (in the dim state), which has been impossible to do in a single sources until now.

  9. Nonlinear optical studies and structure-activity relationship of chalcone derivatives with in silico insights

    Science.gov (United States)

    Kar, Swayamsiddha; Adithya, K. S.; Shankar, Pruthvik; Jagadeesh Babu, N.; Srivastava, Sailesh; Nageswara Rao, G.

    2017-07-01

    Nine chalcones were prepared via Claisen-Schmidt condensation, and characterized by UV-vis, IR, 1H NMR, 13C NMR and mass spectrometry. One of the representative member 4-NDM-TC has been studied via single crystal XRD and the TGA/DTA technique. SHG efficiency and NLO susceptibilities of the chalcones have been evaluated by the Kurtz and Perry method and Degenerate Four Wave Mixing techniques respectively. 3-Cl-4‧-HC was noted to possess SHG efficiency 1.37 times that of urea while 4-NDM-TC returned the highest third order NLO susceptibilities with respect to CS2. In silico studies help evaluate various physical parameters, in correlating the observed activities. In conclusion, the structure-activity relationship was derived based on the in silico and experimental results for the third order NLO susceptibilities.

  10. 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...

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Mengyang Li

    2017-01-01

    Full Text Available 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.

  13. Insights on the Spectral Signatures of Stellar Activity and Planets from PCA

    Science.gov (United States)

    Davis, Allen B.; Cisewski, Jessi; Dumusque, Xavier; Fischer, Debra A.; Ford, Eric B.

    2017-09-01

    Photospheric velocities and stellar activity features such as spots and faculae produce measurable radial velocity signals that currently obscure the detection of sub-meter-per-second planetary signals. However, photospheric velocities are imprinted differently in a high-resolution spectrum than are Keplerian Doppler shifts. Photospheric activity produces subtle differences in the shapes of absorption lines due to differences in how temperature or pressure affects the atomic transitions. In contrast, Keplerian Doppler shifts affect every spectral line in the same way. With a high enough signal-to-noise (S/N) and resolution, statistical techniques can exploit differences in spectra to disentangle the photospheric velocities and detect lower-amplitude exoplanet signals. We use simulated disk-integrated time-series spectra and principal component analysis (PCA) to show that photospheric signals introduce spectral line variability that is distinct from that of Doppler shifts. We quantify the impact of instrumental resolution and S/N for this work.

  14. 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.

  15. 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...

  16. Alternative Woods for Aging Distillates -An Insight into Their Phenolic Profiles and Antioxidant Activities

    OpenAIRE

    Rodríguez,Roberto; Suárez, Belén; Diñeiro, Yolanda; Valle, Paula; Picinelli, A.M. (Anna)

    2012-01-01

    Work has commenced on the study and characterization of wood native species (oak, chestnut, cherry, alder, ash, and beech), employed to a minor extent in enology, for their application in the elaboration of distillates. To this end, furanic and low molecular weight phenol compounds, total phenolic content, and antioxidant activity in alcoholic extracts by maceration of wood chips at 2 toasting levels were studied. Significant differences between samples, technologically relevant, were due bot...

  17. Simultaneous Activation of Multiple Memory Systems during Learning: Insights from Electrophysiology and Modeling

    Science.gov (United States)

    2010-06-01

    following OFC damage. In addiction , OFC activation is seen in response to drug stimuli that elicit craving , perhaps consistent with its hypothesized role in...34 and has been extensively studied in the context of drug addiction and more recently in behavioral studies investigating its role in goal-directed...encoding expected reward. For reviews on the role of the OFC in addiction , see Everitt et al. (2007). For reviews regarding the OFC in normal

  18. 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.

  19. 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.

  20. Cloud droplet activation mechanisms of amino acid aerosol particles: insight from molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Xin Li

    2013-07-01

    Full Text Available Atmospheric amino acids constitute a large fraction of water-soluble organic nitrogen compounds in aerosol particles, and have been confirmed as effective cloud condensation nuclei (CCN materials in laboratory experiments. We present a molecular dynamics (MD study of six amino acids with different structures and chemical properties that are relevant to the remote marine atmospheric aerosol–cloud system, with the aim of investigating the detailed mechanism of their induced changes in surface activity and surface tension, which are important properties for cloud drop activation. Distributions and orientations of the amino acid molecules are studied; these l-amino acids are serine (SER, glycine (GLY, alanine (ALA, valine (VAL, methionine (MET and phenylalanine (PHE and are categorised as hydrophilic and amphiphilic according to their affinities to water. The results suggest that the presence of surface-concentrated amphiphilic amino acid molecules give rise to enhanced Lennard–Jones repulsion, which in turn results in decreased surface tension of a planar interface and an increased surface tension of the spherical interface of droplets with diameters below 10 nm. The observed surface tension perturbation for the different amino acids under study not only serves as benchmark for future studies of more complex systems, but also shows that amphiphilic amino acids are surface active. The MD simulations used in this study reproduce experimental results of surface tension measurements for planar interfaces and the method is therefore applicable for spherical interfaces of nano-size for which experimental measurements are not possible to conduct.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

    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 (td,E) and hydroxyl-radical oxidation half-lives (tOH,E) in sunlit surface waters. The td,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas tOH,E ranges from 3.24h to 33.6h, 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. Copyright © 2015. Published by Elsevier B.V.

  4. 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

  5. Insights into seasonal active layer dynamics by monitoring relative velocity changes using ambient seismic noise

    Science.gov (United States)

    James, S. R.; Knox, H. A.; Cole, C. J.; Abbott, R. E.; Screaton, E.

    2016-12-01

    Seasonal freeze and thaw of the active layer above permafrost results in dramatic changes in seismic velocity. We used daily cross correlations of ambient seismic noise recorded at Poker Flat Research Range in central Alaska to create a nearly continuous 2-year record of relative velocity changes. This analysis required that we modify the Moving Window Cross-spectral Analysis technique used in the Python package MSNoise to reduce the occurrence of cycle skipping. Results show relative velocity variations follow a seasonal pattern, where velocities decrease in late spring through the summer months and increase through the fall and winter months. This timing is consistent with active layer freeze and thaw in this region. These results were compared to a suite of ground- and satellite-based measurements to identify relationships. A decrease in relative velocities in late spring closely follows the timing of snow melt recorded in nearby ground temperatures and snow-depth logs. This transition also aligns with a decrease in the Normalized Difference Snow Index (NDSI) derived from multi-temporal Landsat 8 satellite imagery collected over the study site. A gradual increase in relative velocity through the fall months occurs when temperatures below ground surface remain near zero. We suggest this is due to latent heat feedbacks that keep temperatures constant while active layer velocities increase from continued ice formation. This highlights the value in velocity variations for capturing details on the freezing process. In addition, spatial variations in the magnitude of velocity changes are consistent with thaw probe surveys. Exploring relationships with remote sensing may allow indirect measurements of thaw over larger areas and further surface wave analysis may allow for thickness evolution measurements. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for

  6. 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.

  7. 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.

  8. 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.

  9. Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved

    Science.gov (United States)

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika

    2014-01-01

    Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet. PMID:24761002

  10. Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.

    Science.gov (United States)

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika; Gamba, Gerardo

    2014-06-15

    Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet. Copyright © 2014 the American Physiological Society.

  11. New insights into [FeFe] hydrogenase activation and maturase function.

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    Jon M Kuchenreuther

    Full Text Available [FeFe] hydrogenases catalyze H(2 production using the H-cluster, an iron-sulfur cofactor that contains carbon monoxide (CO, cyanide (CN(-, and a dithiolate bridging ligand. The HydE, HydF, and HydG maturases assist in assembling the H-cluster and maturing hydrogenases into their catalytically active form. Characterization of these maturases and in vitro hydrogenase activation methods have helped elucidate steps in the H-cluster biosynthetic pathway such as the HydG-catalyzed generation of the CO and CN(- ligands from free tyrosine. We have refined our cell-free approach for H-cluster synthesis and hydrogenase maturation by using separately expressed and purified HydE, HydF, and HydG. In this report, we illustrate how substrates and protein constituents influence hydrogenase activation, and for the first time, we show that each maturase can function catalytically during the maturation process. With precise control over the biomolecular components, we also provide evidence for H-cluster synthesis in the absence of either HydE or HydF, and we further show that hydrogenase activation can occur without exogenous tyrosine. Given these findings, we suggest a new reaction sequence for the [FeFe] hydrogenase maturation pathway. In our model, HydG independently synthesizes an iron-based compound with CO and CN(- ligands that is a precursor to the H-cluster [2Fe](H subunit, and which we have termed HydG-co. We further propose that HydF is a transferase that stabilizes HydG-co and also shuttles the complete [2Fe](H subcluster to the hydrogenase, a translocation process that may be catalyzed by HydE. In summary, this report describes the first example of reconstructing the [FeFe] hydrogenase maturation pathway using purified maturases and subsequently utilizing this in vitro system to better understand the roles of HydE, HydF, and HydG.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Insights into the emission reductions of multiple unintentional persistent organic pollutants from industrial activities.

    Science.gov (United States)

    Liu, Guorui; Zheng, Minghui; Jiang, Xiaoxu; Jin, Rong; Zhao, Yuyang; Zhan, Jiayu

    2016-02-01

    Industrial activities result in unintentional production of multiple types of persistent organic pollutants (POPs) at various concentrations. Because of the potential adverse effect of these POPs on the environment, biota and human health, methods for controlling emission of POPs are required. Development and application of techniques for controlling emissions of POPs can be a technical and economic burden for the industry involved. Therefore, from the point of view of cost-benefit analysis, reducing emissions of multiple pollutants at the same time is optimal for sustainable industrial development. Although techniques have been developed for reducing the emissions of individual POPs, such as dioxins, further work is required on multi-POP control emissions from industrial activities. This paper discusses three important aspects that need to be taken to achieve multi-POP control. These aspects include the establishment of a comprehensive system for evaluating the risk from emissions of multiple POPs, determination of indicators for total emissions of multiple POPs, and the preparation and application of functional materials to inhibit formation of multiple POPs. These discussion might be helpful for the future research on the multi-POP control in industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Structure of a diguanylate cyclase from Thermotoga maritima: insights into activation, feedback inhibition and thermostability.

    Directory of Open Access Journals (Sweden)

    Angeline Deepthi

    Full Text Available Large-scale production of bis-3'-5'-cyclic-di-GMP (c-di-GMP would facilitate biological studies of numerous bacterial signaling pathways and phenotypes controlled by this second messenger molecule, such as virulence and biofilm formation. C-di-GMP constitutes also a potentially interesting molecule as a vaccine adjuvant. Even though chemical synthesis of c-di-GMP can be done, the yields are incompatible with mass-production. tDGC, a stand-alone diguanylate cyclase (DGC or GGDEF domain from Thermotoga maritima, enables the robust enzymatic production of large quantities of c-di-GMP. To understand the structural correlates of tDGC thermostability, its catalytic mechanism and feedback inhibition, we determined structures of an active-like dimeric conformation with both active (A sites facing each other and of an inactive dimeric conformation, locked by c-di-GMP bound at the inhibitory (I site. We also report the structure of a single mutant of tDGC, with the R158A mutation at the I-site, abolishing product inhibition and unproductive dimerization. A comparison with structurally characterized DGC homologues from mesophiles reveals the presence of a higher number of salt bridges in the hyperthermophile enzyme tDGC. Denaturation experiments of mutants disrupting in turn each of the salt bridges unique to tDGC identified three salt-bridges critical to confer thermostability.

  19. 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.

  20. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

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    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  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. Some Insights to the Reuse of Dredged Marine Soils by Admixing with Activated Steel Slag

    Directory of Open Access Journals (Sweden)

    Chee-Ming Chan

    2014-01-01

    Full Text Available Regular dredging is necessary for the development of coastal regions and the maintenance of shipping channels. The dredging process dislodges sediments from the seabed, and the removed materials, termed dredged marine soils, are generally considered a geowaste for dumping. However, disposal of the dredged soils offshores can lead to severe and irreversible impact on the marine ecosystem, while disposal on land often incurs exorbitant costs with no guarantee of zero-contamination. It is therefore desirable to reuse the material, and one option is solidification with another industrial waste, that is, steel slag. This paper describes the exploratory work of admixing dredged marine soil with activated steel slag for improvement of the mechanical properties. An optimum activation concentration of NaOH was introduced to the soil-slag mixture for uniform blending. Specimens were prepared at different mix ratios then left to cure for up to 4 weeks. The unconfined compressive strength test was conducted to monitor the changes in strength at predetermined intervals. It was found that the strength does not necessarily increase with higher steel slag content, indicating an optimum slag content required for the maximum solidification effect to take place. Also, regardless of the slag content, longer curing time produces greater strength gain. In conclusion, steel slag addition to dredged sediments can effectively strengthen the originally weak soil structure by both the “cementation” and “filler” effects, though the combined effects were not distinguished in the present study.

  3. 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.

  4. 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

  5. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit.

    Science.gov (United States)

    Brites, Fernando; Martin, Maximiliano; Guillas, Isabelle; Kontush, Anatol

    2017-12-01

    Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation. Circulating high-density lipoprotein (HDL) particles, primarily small, dense, protein-rich HDL3, provide potent protection of LDL from oxidative damage by free radicals, resulting in the inhibition of the generation of pro-inflammatory oxidized lipids. HDL-mediated inactivation of lipid hydroperoxides involves their initial transfer from LDL to HDL and subsequent reduction to inactive hydroxides by redox-active Met residues of apolipoprotein A-I. Several HDL-associated enzymes are present at elevated concentrations in HDL3 relative to large, light HDL2 and can be involved in the inactivation of short-chain oxidized phospholipids. Therefore, HDL represents a multimolecular complex capable of acquiring and inactivating proatherogenic lipids. Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

  6. 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.

  7. 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.

  8. Translational Insights Into Peroxisome Proliferator-Activated Receptors in Experimental Acute Pancreatitis.

    Science.gov (United States)

    Huang, Wei; Szatmary, Peter; Wan, Meihua; Bharucha, Shameena; Awais, Muhammad; Tang, Wenfu; Criddle, David N; Xia, Qing; Sutton, Robert

    2016-02-01

    Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas frequently associated with metabolic causes, contributing factors, or consequences, including hypertriglyceridemia, obesity, and disorders of intermediary metabolism, respectively. To date, there is no specific therapy for this disease. Future optimal therapy should correct both inflammatory and metabolic components of the disease. Peroxisome proliferator-activated receptors (PPARs) are lipid-sensing nuclear receptors that control inflammatory and metabolic pathways via ligand-dependent and ligand-independent mechanisms. There are 3 known subtypes, PPAR-α, PPAR-β/δ, and PPAR-γ, which are differentially expressed in various tissues. The PPARs interact closely with other transcription factors such as nuclear factor κB and signal tranducers and activators of transcription that have pivotal roles in the pathobiology of AP. In this comprehensive review, we summarize the role of PPARs in AP, highlighting important in vitro and in vivo experimental findings. Finally, we propose future research directions as well as potential translational use of PPAR agonists in the treatment of AP.

  9. Insights into the role of hepatocyte PPARα activity in response to fasting.

    Science.gov (United States)

    Régnier, Marion; Polizzi, Arnaud; Lippi, Yannick; Fouché, Edwin; Michel, Géraldine; Lukowicz, Céline; Smati, Sarra; Marrot, Alain; Lasserre, Frédéric; Naylies, Claire; Batut, Aurélie; Viars, Fanny; Bertrand-Michel, Justine; Postic, Catherine; Loiseau, Nicolas; Wahli, Walter; Guillou, Hervé; Montagner, Alexandra

    2017-07-31

    The liver plays a central role in the regulation of fatty acid metabolism. Hepatocytes are highly sensitive to nutrients and hormones that drive extensive transcriptional responses. Nuclear hormone receptors are key transcription factors involved in this process. Among these factors, PPARα is a critical regulator of hepatic lipid catabolism during fasting. This study aimed to analyse the wide array of hepatic PPARα-dependent transcriptional responses during fasting. We compared gene expression in male mice with a hepatocyte specific deletion of PPARα and their wild-type littermates in the fed (ad libitum) and 24-h fasted states. Liver samples were acquired, and transcriptome and lipidome analyses were performed. Our data extended and confirmed the critical role of hepatocyte PPARα as a central for regulator of gene expression during starvation. Interestingly, we identified novel PPARα-sensitive genes, including Cxcl-10, Rab30, and Krt23. We also found that liver phospholipid remodelling was a novel fasting-sensitive pathway regulated by PPARα. These results may contribute to investigations on transcriptional control in hepatic physiology and underscore the clinical relevance of drugs that target PPARα in liver pathologies, such as non-alcoholic fatty liver disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Mechanistic insight into formation and changes of nanoparticles in MgF2 sols evidenced by liquid and solid state NMR.

    Science.gov (United States)

    Karg, M; Scholz, G; König, R; Kemnitz, E

    2012-02-28

    The fluorolytic sol-gel reaction of magnesium methoxide with HF in methanol was studied by (19)F, (1)H and (13)C liquid and solid state NMR. In (19)F NMR five different species were identified, three of which belong to magnesium fluoride nanoparticles, i.e. NMR gave access to local structures of solid particles in suspensions. The long-term evolution of (19)F signals was followed and along with (19)F MAS NMR experiments of sols rotating at 13 kHz mechanistic insights into the ageing processes were obtained.

  11. 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

  12. 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

  13. 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.

  14. Insights on glucocorticoid receptor activity modulation through the binding of rigid steroids.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    Full Text Available BACKGROUND: The glucocorticoid receptor (GR is a transcription factor that regulates gene expression in a ligand-dependent fashion. This modular protein is one of the major pharmacological targets due to its involvement in both cause and treatment of many human diseases. Intense efforts have been made to get information about the molecular basis of GR activity. METHODOLOGY/PRINCIPAL FINDINGS: Here, the behavior of four GR-ligand complexes with different glucocorticoid and antiglucocorticoid properties were evaluated. The ability of GR-ligand complexes to oligomerize in vivo was analyzed by performing the novel Number and Brightness assay. Results showed that most of GR molecules form homodimers inside the nucleus upon ligand binding. Additionally, in vitro GR-DNA binding analyses suggest that ligand structure modulates GR-DNA interaction dynamics rather than the receptor's ability to bind DNA. On the other hand, by coimmunoprecipitation studies we evaluated the in vivo interaction between the transcriptional intermediary factor 2 (TIF2 coactivator and different GR-ligand complexes. No correlation was found between GR intranuclear distribution, cofactor recruitment and the homodimerization process. Finally, Molecular determinants that support the observed experimental GR LBD-ligand/TIF2 interaction were found by Molecular Dynamics simulation. CONCLUSIONS/SIGNIFICANCE: The data presented here sustain the idea that in vivo GR homodimerization inside the nucleus can be achieved in a DNA-independent fashion, without ruling out a dependent pathway as well. Moreover, since at least one GR-ligand complex is able to induce homodimer formation while preventing TIF2 coactivator interaction, results suggest that these two events might be independent from each other. Finally, 21-hydroxy-6,19-epoxyprogesterone arises as a selective glucocorticoid with potential pharmacological interest. Taking into account that GR homodimerization and cofactor recruitment are

  15. 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)

  16. Learning shapes spontaneous activity itinerating over memorized states.

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Insights into the evolution of tectonically-active glaciated mountain ranges from digital elevation model analyses

    Science.gov (United States)

    Brocklehurst, S. H.; Whipple, K. X.

    2003-12-01

    Glaciers have played an important role in the development of most active mountain ranges around the world during the Quaternary, but the interaction between glacial erosion (as modulated by climate change) and tectonic processes is poorly understood. The so-called glacial buzzsaw hypothesis (Brozovic et al., 1997) proposes that glaciers can incise as rapidly as the most rapid rock uplift rates, such that glaciated landscapes experiencing different rock uplift rates but the same snowline elevation will look essentially the same, with mean elevations close to the snowline. Digital elevation model-based analyses of the glaciated landscapes of the Nanga Parbat region, Pakistan, and the Southern Alps, New Zealand, lend some support to this hypothesis, but also reveal considerably more variety to the landscapes of glaciated, tectonically-active mountain ranges. Larger glaciers in the Nanga Parbat region maintain a low downvalley gradient and valley floor elevations close to the snowline, even in the face of extremely rapid rock uplift. However, smaller glaciers steepen in response to rapid uplift, similar to the response of rivers. A strong correlation between the height of hillslopes rising from the cirque floors and rock uplift rates implies that erosion processes on hillslopes cannot initially keep up with more rapid glacial incision rates. It is these staggering hillslopes that permit mountain peaks to rise above 8000m. The glacial buzzsaw hypothesis does not describe the evolution of the Southern Alps as well, because here mean elevations rise in areas of more rapid rock uplift. The buzzsaw hypothesis may work well in the Nanga Parbat region because the zone of rapid rock uplift is structurally confined to a narrow region. Alternatively, the Southern Alps may not have been rising sufficiently rapidly or sufficiently long for the glacial buzzsaw to be imposed outside the most rapidly uplifting region, around Mount Cook. The challenge now is to understand in detail

  19. Structural insights into ligand-induced activation of the insulin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Ward, C.; Lawrence, M.; Streltsov, V.; Garrett, T.; McKern, N.; Lou, M.-Z.; Lovrecz, G.; Adams, T. (CSIRO); (WEHIMR)

    2008-04-29

    The current model for insulin binding to the insulin receptor proposes that there are two binding sites, referred to as sites 1 and 2, on each monomer in the receptor homodimer and two binding surfaces on insulin, one involving residues predominantly from the dimerization face of insulin (the classical binding surface) and the other residues from the hexamerization face. High-affinity binding involves one insulin molecule using its two surfaces to make bridging contacts with site 1 from one receptor monomer and site 2 from the other. Whilst the receptor dimer has two identical site 1-site 2 pairs, insulin molecules cannot bridge both pairs simultaneously. Our structures of the insulin receptor (IR) ectodomain dimer and the L1-CR-L2 fragments of IR and insulin-like growth factor receptor (IGF-1R) explain many of the features of ligand-receptor binding and allow the two binding sites on the receptor to be described. The IR dimer has an unexpected folded-over conformation which places the C-terminal surface of the first fibronectin-III domain in close juxtaposition to the known L1 domain ligand-binding surface suggesting that the C-terminal surface of FnIII-1 is the second binding site involved in high-affinity binding. This is very different from previous models based on three-dimensional reconstruction from scanning transmission electron micrographs. Our single-molecule images indicate that IGF-1R has a morphology similar to that of IR. In addition, the structures of the first three domains (L1-CR-L2) of the IR and IGF-1R show that there are major differences in the two regions governing ligand specificity. The implications of these findings for ligand-induced receptor activation will be discussed. This review summarizes the key findings regarding the discovery and characterization of the insulin receptor, the identification and arrangement of its structural domains in the sequence and the key features associated with ligand binding. The remainder of the review

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Mechanical behaviour of the Krafla geothermal reservoir: Insight into an active magmatic hydrothermal system

    Science.gov (United States)

    Eggertsson, Guðjón H.; Lavallée, Yan; Kendrick, Jackie E.

    2017-04-01

    Krafla volcano, located in North-East Iceland, holds an active magmatic hydrothermal system. Since 1978, this system has been exploited for geothermal energy. Today it is exploited by Landsvirkjun National Power of Iceland and the system is generating 60 MWg from 18 wells, tapping into fluids at 200-300°C. In order to meet further demands of environmentally sustainable energy, Landsvirkjun aims to drill deeper and source fluids in the super-heated, super high-enthalpy system which resides deeper (at 400-600°C). In relation to this, the first well of the Icelandic Deep Drilling Project (IDDP) was drilled in Krafla in 2009. Drilling stopped at a depth of 2.1 km, when the drill string penetrated a rhyolitic magma body, which could not be bypassed despite attempts to side-track the well. This pioneering effort demonstrated that the area close to magma had great energy potential. Here we seek a constraint on the mechanical properties of reservoir rocks overlying the magmatic systems to gain knowledge on these systems to improve energy extraction. During two field surveys in 2015 and 2016, and through information gathered from drilling of geothermal wells, five main rock types were identified and sampled [and their porosities (i.e., storage capacities) where determined with a helium-pycnometer]: basalts (5-60% porosity), hyaloclastites (geothermal reservoir. Uniaxial and triaxial compressive strength tests have been carried out, as well as indirect tensile strength tests using the Brazilian disc method, to measure the rock strengths. The results show that the rock strength is inversely proportional to the porosity and strongly affected by the abundance of microcracks; some of the rocks are unusually weak considering their porosities, especially at low effective pressure as constrained at Krafla. The results also show that the porous lithologies may undergo significant compaction at relatively low loads (i.e., depth). Integration of the observed mechanical behaviour and

  15. Environmental influences on activity patterns in altered states of consciousness.

    Science.gov (United States)

    De Weer, A-S; Da Ros, M; Berré, J; Mélot, C; Goldman, S; Peigneux, P

    2011-12-01

    To evaluate in disorders of consciousness (DOC) circadian variations in motor patterns and their possible synchronization with physiologically regulated light variations and/or a social environmental factor, i.e. presence and actions of other persons. Actimetric and ambient light levels recordings were obtained during 4-9 days in two patients with traumatic brain injury (TB1 and TB2) in a minimally conscious state (MCS), one MCS (AI1) and one comatose (AI2) anoxic-ischaemic patients. Environmental changes were automatically recorded using a video system. Minute light variations correlated with motor activity in all patients. However, motor activity was significantly higher during day than nighttime and correlated with social environmental changes, in patients TB1 and TB2 only. Night-day circadian variations in motor activity patterns and influence of social stimulations were observed in traumatic MCS patients only. Nonetheless, rapid light variations may temporarily promote increased arousal, and consequently motor activity, in all DOCs. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  16. 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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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

  19. The HhoA protease from Synechocystis sp. PCC 6803 - Novel insights into structure and activity regulation.

    Science.gov (United States)

    Hall, Michael; Wagner, Raik; Lam, Xuan Tam; Funk, Christiane; Persson, Karina

    2017-06-01

    Proteases play a vital role in the removal of proteins, which become damaged due to temperature or oxidative stress. Important to this process in the cyanobacterium Synechocystis sp. PCC6803 is the family of Deg/HtrA proteases; HhoA (sll1679), HhoB (sll1427) and HtrA (slr1204). While previous studies have elucidated the structures of Deg/HtrA proteases from Escherichia coli and from the chloroplast of the higher plant Arabidopsis thaliana, no structural data have been available for any Deg/HtrA protease from cyanobacteria, the evolutionary ancestor of the chloroplast. To gain a deeper insight into the molecular mechanisms and regulation of these proteins we have solved the structure of the Synechocystis HhoA protease in complex with a co-purified peptide by X-ray crystallography. HhoA assembles into stable trimers, mediated by its protease domain and further into a cage-like hexamer by a novel interaction between the PDZ domains of opposing trimers. Each PDZ domain contains two loops for PDZ-PDZ formation: interaction clamp one and two (IC1, IC2). IC1 interacts with IC2 on the opposing PDZ domain and vice versa. Our structure shows a peptide bound to a conserved groove on the PDZ domain and the properties of this pocket suggest that it binds substrate proteins as well as the neo C-termini of cleaved substrates. In agreement with previous studies showing the proteolytic activity of HhoA to be activated by Ca(2+) or Mg(2+), binding of divalent metal ions to the central channel of the trimer by the L1 activation loop was observed. Copyright © 2016. Published by Elsevier Inc.

  20. 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.

  1. 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?

  2. Structural Insights of the Cysteine Protease Heynein from Induction and Characterization of Non-native Intermediate States

    Directory of Open Access Journals (Sweden)

    Basant K. Patel

    2010-12-01

    Full Text Available Cysteine proteases are vital to cell physiology and many plants secrete these proteases for defense purposes. Many recent studies have reported unusually high stabilities for several plant cysteine proteases which possibly enable these proteases to function under adverse environmental conditions. Here, we have examined the conformational features of a new plant cysteine protease heynein using spectroscopic tools to understand the basis for its robust functional stability. The studies revealed structural integrity over a wide range of pH (2.5-12.0, temperature (65 oC and urea (8M. However, at pH 2.0, the protein gets acid-unfolded (UA -state with exposed hydrophobic patches, which upon addition of more protons (pH 0.5 or anions (0.5 M KCl and 0.2 M Na2 SO4 yields conformationally distinct refolded intermediates respectively termed: A-, I 1 - and I 2 -states. Strikingly, a high methanol level drives the UA -state into a predominantly -sheet rich conformation (O-state. We observed three-state unfolding kinetics of the I 2 -state by urea, possibly suggesting presence of two domains in the heynein molecule.

  3. 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.

  4. Shallow Lunar Seismic Activity and the Current Stress State of the Moon

    Science.gov (United States)

    Watters, Thomas R.; Weber, Renee C.; Collins, Geoffrey C.; Johnson, Catherine L.

    2017-01-01

    A vast, global network of more than 3200 lobate thrust fault scarps has been revealed in high resolution Lunar Reconnaissance Orbiter Camera (LROC) images. The fault scarps are very young, less than 50 Ma, based on their small scale and crisp appearance, crosscutting relations with small-diameter impact craters, and rates of infilling of associated small, shallow graben and may be actively forming today. The population of young thrust fault scarps provides a window into the recent stress state of the Moon and offers insight into the origin of global lunar stresses. The distribution of orientations of the fault scarps is non-random, inconsistent with isotropic stresses from late-stage global contraction as the sole source of stress. Modeling shows that tidal stresses contribute significantly to the current stress state of the lunar crust. Tidal stresses (orbital recession and diurnal tides) superimposed on stresses from global contraction result in non-isotropic compressional stress and may produce thrust faults consistent with lobate scarp orientations. At any particular point on the lunar surface, peak compressive stress will be reached at a certain time in the diurnal cycle. Coseismic slip events on currently active thrust faults are expected to be triggered when peak stresses are reached. Analysis of the timing of the 28 the shallow moonquakes recorded by the Apollo seismic network shows that 19 indeed occur when the Moon is closer to apogee, while only 9 shallow events occur when the Moon is closer to perigee. Here we report efforts to refine the model for the current stress state of the Moon by investigating the contribution of polar wander. Progress on relocating the epicentral locations of the shallow moonquakes using an algorithm designed for sparse networks is also reported.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

    gener- ation times of ultra-slow microbial life from millennial toward decadal time scales. The obtained data will therefore influence our view of microbial activities on global element cycling over geologic time scales. Controlling factors of the microbial community size and its activity seemed...

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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...

  17. 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.

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

    Science.gov (United States)

    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/de...

  19. 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.

  20. Molecular modeling study on the tubulin-binding modes of epothilone derivatives: Insight into the structural basis for epothilones activity.

    Science.gov (United States)

    Jiménez, Verónica A; Alderete, Joel B; Navarrete, Karen R

    2017-06-20

    Molecular dynamics (MD) simulations were employed to study the tubulin-binding modes of 20 epothilone derivatives spanning a wide range of antitumor activity. Trajectory analysis revealed that active ligands shared a common region of association and similar binding poses compared to the high-resolution crystal structure of the tubulin complex with epothilone A, the stathmin-like protein RB3, and tubulin tyrosine ligase (PDB code 4I50). Conformational analysis of epothilones in aqueous solution and tubulin-bound states indicated that the bound conformations of active species can be found to a significant extent within the ensemble of conformers available in aqueous solution. On the other hand, inactive derivatives were unable to adopt bound-like conformations in aqueous solution, thus requiring an extensive conformational pre-organization to accomplish an effective interaction with the tubulin receptor. Additionally, MD results revealed that epothilone binding-induced structuring of the M-loop and local flexibility changes in protein regions involved in interdimeric contacts that are relevant for microtubule stabilization. These results provide novel, valuable structural information to increase understanding about the underlying molecular aspects of epothilones activity and support further work on the search for new active tubulin-binding agents. © 2017 John Wiley & Sons A/S.

  1. 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.

  2. Structural and dynamic insights into the free energy barrier for activation loop rearrangement in FGFR1 tyrosine kinase

    OpenAIRE

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J; Davies, Gareth,; Holdgate, Geoffrey A.; Phillips, Chris; Tucker, Julie A.; Norman, Richard A; Scott, Andrew D; Higazi, Daniel R.; Lowe, David; Thompson, Gary S.; Breeze, Alexander L.

    2015-01-01

    This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms8877 Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called ‘DFG flip’. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a ‘DFG-out’ state. Here we use conformationally...

  3. 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.)

  4. 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.

  5. Water-temperature data acquisition activities in the United States

    Science.gov (United States)

    Pauszek, F.H.

    1972-01-01

    Water Data Coordination, U.S. Geological Survey, and published in the "Catalog of Information on Water Data, Index to Water Quality Section, Edition 1970." This is one of four indexes, each of which is a separate section of the Catalog. Three of the indexes, "Index to Water-Quality Section," "Index to Surface-Water Section," and "Index to Ground-.Water Stations," contain information on data acquired on a recurrent basis at specific locations for a period of 3 years or more. The fourth section, "Index to Areal Investigations and Miscellaneous Activities," is concerned with specific projects or shorter-term data activities that involve field or laboratory measurements or observations not included in any other section of the Catalog. The Catalog is a record of activities throughout the country (and in some places along the international border between the United States and Canada) conducted by Federal and non-Federal agencies engaged in the acquisition of water data and who furnish such information for presentation in the Catalog. The Catalog itself is an outgrowth of an assignment to the Department of the Interior and in turn to the Geological Survey, by the Office of Management and Budget, through the medium of OMB Circular A-67. This Circular states in part that one of the assigned responsibilities will be maintenance of a "central catalog of information on...water data and on Federal activities being planned or conducted to acquire such data." As an extension of this activity, non-Federal agencies are solicited to participate in the program. In this report, information is presented by means of tables and illustrations preceded by brief explanations. It includes the agencies collecting the data, the number of stations located on surface and ground waters where temperature measurements are made, the distribution of stations by States and by the 21 regions of the Water Resources Council (WRC) (a Federal agency created in accordance with the Water Resources Planning Act of

  6. 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

  7. Insights Into Intimate Partner Violence in Pregnancy: Findings From a Cross-Sectional Study in Two States in Nigeria.

    Science.gov (United States)

    Ansari, Umaira; Cobham, Bassy; Etim, Egbai Moses; Ahamad, Hauwa Mohammad; Owan, Nchajeno Otabai; Tijani, Yaya; Cockcroft, Anne; Andersson, Neil

    2016-04-27

    A household survey and focus group discussions examined the frequency and risk factors for physical intimate partner violence (IPV) during pregnancy in two Nigerian states. Some 22% of women in Cross River and 9% in Bauchi reported IPV in their last pregnancy. The risk was higher in communities where more women reported IPV in the past year and lower among less poor women with more educated partners. Women were more likely to experience IPV in pregnancy if they had an income and decided how to spend it. Efforts to reduce IPV in pregnancy should involve communities as well as individuals. © The Author(s) 2016.

  8. Insights into Solid-State Electron Transport through Proteins from Inelastic Tunneling Spectroscopy: The Case of Azurin.

    Science.gov (United States)

    Yu, Xi; Lovrincic, Robert; Sepunaru, Lior; Li, Wenjie; Vilan, Ayelet; Pecht, Israel; Sheves, Mordechai; Cahen, David

    2015-10-27

    Surprisingly efficient solid-state electron transport has recently been demonstrated through "dry" proteins (with only structural, tightly bound H2O left), suggesting proteins as promising candidates for molecular (bio)electronics. Using inelastic electron tunneling spectroscopy (IETS), we explored electron-phonon interaction in metal/protein/metal junctions, to help understand solid-state electronic transport across the redox protein azurin. To that end an oriented azurin monolayer on Au is contacted by soft Au electrodes. Characteristic vibrational modes of amide and amino acid side groups as well as of the azurin-electrode contact were observed, revealing the azurin native conformation in the junction and the critical role of side groups in the charge transport. The lack of abrupt changes in the conductance and the line shape of IETS point to far off-resonance tunneling as the dominant transport mechanism across azurin, in line with previously reported (and herein confirmed) azurin junctions. The inelastic current and hence electron-phonon interaction appear to be rather weak and comparable in magnitude with the inelastic fraction of tunneling current via alkyl chains, which may reflect the known structural rigidity of azurin.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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,...

  15. 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.

  16. Caffeine consumption among active duty United States Air Force personnel.

    Science.gov (United States)

    Knapik, Joseph J; Austin, Krista G; McGraw, Susan M; Leahy, Guy D; Lieberman, Harris R

    2017-07-01

    Data from the National Health and Nutrition Examination Survey (NHANES) indicated that 89% of Americans regularly consumed caffeinated products, but these data did not include military personnel. This cross-sectional study examined caffeine consumption prevalence, amount of daily consumption, and factors associated with caffeine intake in active duty United States (US) Air Force personnel. Service members (N = 1787) stationed in the US and overseas completed a detailed questionnaire describing their intake of caffeine-containing products in addition to their demographic, lifestyle, and military characteristics. Overall, 84% reported consuming caffeinated products ≥1 time/week with caffeine consumers ingesting a mean ± standard error of 212 ± 9 mg/day (224 ± 11 mg/day for men, 180 ± 12 mg/day for women). The most commonly consumed caffeinated products (% users) were sodas (56%), coffee (45%), teas (36%), and energy drinks (27%). Multivariate logistic regression modeling indicated that characteristics independently associated with caffeine consumption (≥1 time/week) included older age, ethnicity other than black, tobacco use, less aerobic training, and less sleep; energy drink use was associated with male gender, younger age, tobacco use, and less sleep. Compared to NHANES data, the prevalence of caffeine consumption in Air Force personnel was similar but daily consumption (mg/day) was higher. Published by Elsevier Ltd.

  17. 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.

  18. Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

    Science.gov (United States)

    Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

    2016-11-01

    The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

  19. 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.

  20. Analysis of medieval mtDNA from Napole cemetery provides new insights into the early history of Polish state.

    Science.gov (United States)

    Płoszaj, Tomasz; Jędrychowska-Dańska, Krystyna; Masłowska, Alicja; Kozłowski, Tomasz; Chudziak, Wojciech; Bojarski, Jacek; Robaszkiewicz, Agnieszka; Witas, Henryk W

    2017-02-01

    Contemporary historical anthropology and classical archaeology are concerned not only with such fundamental issues as the origins of ancient human populations and migration routes, but also with the formation and development of inter-population relations and the mixing of gene pools as a result of inter-breeding between individuals representing different cultural units. The contribution of immigrants to the analysed autochthonous population and their effect on the gene pool of that population has proven difficult to evaluate with classical morphological methods. The burial of one individual in the studied Napole cemetery located in central Poland had the form of a chamber grave, which is typical of Scandinavian culture from that period. However, this fact cannot be interpreted as absolute proof that the individual (in the biological sense) was allochtonous. This gives rise to the question as to who was actually buried in that cemetery. The ancient DNA results indicate that one of the individuals had an mtDNA haplotype typical of Iron Age northern Europe, which suggests that he could have arrived from that area at a later period. This seems to indirectly confirm the claims of many anthropologists that the development of the early medieval Polish state was significantly and directly influenced by the Scandinavians.

  1. Molecular Insights into Covalently Stained Carious Dentine Using Solid-State NMR and ToF-SIMS.

    Science.gov (United States)

    Almhöjd, Ulrica S; Lingström, Peter; Nilsson, Åke; Norén, Jörgen G; Siljeström, Sandra; Östlund, Åsa; Bernin, Diana

    2017-01-01

    Dyes currently used to stain carious dentine have a limited capacity to discriminate normal dentine from carious dentine, which may result in overexcavation. Consequently, finding a selective dye is still a challenge. However, there is evidence that hydrazine-based dyes, via covalent bonds to functional groups, bind specifically to carious dentine. The aim of this study was to investigate the possible formation of covalent bonds between carious dentine and 15N2-hydrazine and the hydrazine-based dye, 15N2-labelled Lucifer Yellow, respectively. Powdered dentine from extracted carious and normal teeth was exposed to the dyes, and the staining reactions were analysed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), solid-state 13C-labelled nuclear magnetic resonance (NMR) and 15N-NMR spectroscopy. The results showed that 15N2-hydrazine and 15N2-labelled Lucifer Yellow both bind to carious dentine but not to normal dentine. It can thus be concluded that hydrazine-based dyes can be used to stain carious dentine and leave normal dentine unstained. © 2017 S. Karger AG, Basel.

  2. 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...

  3. Which kind of aromatic structures are produced during biomass charring? New insights provided by modern solid-state NMR spectroscopy

    Science.gov (United States)

    Knicker, Heike; Paneque-Carmona, Marina; Velasco-Molina, Marta; de la Rosa, José Maria; León-Ovelar, Laura Regina; Fernandez-Boy, Elena

    2017-04-01

    Intense research on biochar and charcoal of the last years has revealed that depending on the production conditions, the chemical and physical characteristics of their aromatic network can greatly vary. Since such variations are determining the behavior and stability of charred material in soils, a better understanding of the structural changes occurring during their heating and the impact of those changes on their function is needed. One method to characterize pyrogenic organic matter (PyOM) represents solid-state 13C NMR spectroscopy applying the cross polarization (CP) magic angle spinning technique (MAS). A drawback of this technique is that the quantification of NMR spectra of samples with highly condensed and proton-depleted structures is assumed to be bias. Typical samples with such attributes are charcoals produced at temperatures above 700°C under pyrolytic conditions. Commonly their high condensation degree leads to graphenic structures that are not only reducing the CP efficiency but create also a conductive lattice which acts as a shield and prevents the entering of the excitation pulse into the sample during the NMR experiments. Since the latter can damage the NMR probe and in the most cases the obtained NMR spectra show only one broad signal assignable to aromatic C, this technique is rarely applied for characterizing high temperature chars or soot. As a consequence, a more detailed knowledge of the nature of the aromatic ring systems is still missing. The latter is also true for the aromatic domains of PyOM produced at lower temperatures, since older NMR instruments operating at low magnetic fields deliver solid-state 13C NMR spectra with low resolution which turns a more detailed analysis of the aromatic chemical shift region into a challenging task. In order to overcome this disadvantages, modern NMR spectroscopy offers not only instruments with greatly improved resolution but also special pulse sequences for NMR experiments which allow a more

  4. State of stress in exhumed basins and implications for fluid flow: insights from the Illizi Basin, Algeria

    KAUST Repository

    English, Joseph M.

    2017-05-31

    The petroleum prospectivity of an exhumed basin is largely dependent on the ability of pre-existing traps to retain oil and gas volumes during and after the exhumation event. Although faults may act as lateral seals in petroleum traps, they may start to become hydraulically conductive again and enable fluid flow and hydrocarbon leakage during fault reactivation. We constrain the present day in situ stresses of the exhumed Illizi Basin in Algeria and demonstrate that the primary north–south and NW–SE (vertical strike-slip) fault systems in the study area are close to critical stress (i.e. an incipient state of shear failure). By contrast, the overpressured and unexhumed Berkine Basin and Hassi Messaoud areas to the north do not appear to be characterized by critical stress conditions. We present conceptual models of stress evolution and demonstrate that a sedimentary basin with benign in situ stresses at maximum burial may change to being characterized by critical stress conditions on existing fault systems during exhumation. These models are supportive of the idea that the breaching of a closed, overpressured system during exhumation of the Illizi Basin may have been a driving mechanism for the regional updip flow of high-salinity formation water within the Ordovician reservoirs during Eocene–Miocene time. This work also has implications for petroleum exploration in exhumed basins. Fault-bounded traps with faults oriented at a high angle to the maximum principal horizontal stress direction in strike-slip or normal faulting stress regimes are more likely to have retained hydrocarbons in exhumed basins than fault-bounded traps with faults that are more optimally oriented for shear failure and therefore have a greater propensity to become critically stressed during exhumation.

  5. 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

    for GDP release, or, alternatively, the movement is a consequence of release. To gain additional insight into the sequence of events leading to GDP release, we have created a chimeric protein comprised of Escherichia coli NFeoB and the G5 loop from the human Giα1 protein. The protein chimera retains...

  6. Switching activation barriers: new insights in E-field driven processes at the interface: perspectives in physical chemistry and catalysis

    NARCIS (Netherlands)

    Susarrey Arce, A.

    2014-01-01

    The research described in this thesis aimed to explore new concepts in catalysis with the use of a homemade ATR-IR silicon-based microreactor. During this journey we have performed multidisciplinary research at the interface between physics and chemistry. New insights in the fabrication, integration

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Reap around the State: "Best of Reap" Activities.

    Science.gov (United States)

    Indiana State Dept. of Education, Indianapolis. Learning Resources Unit.

    This booklet presents selected activities from elementary, middle, junior high, and senior high schools In Indiana, intended to encourage students to read. It offers ideas for 11 community activities (including guest readers, nursing home reading, and a young author celebration), 14 continuous activities (such as the great book graffiti wall and…

  12. 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.

  13. 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.

  14. Laser cleaning in conservation of stone, metal, and painted artifacts: state of the art and new insights on the use of the Nd:YAG lasers

    Science.gov (United States)

    Siano, S.; Agresti, J.; Cacciari, I.; Ciofini, D.; Mascalchi, M.; Osticioli, I.; Mencaglia, A. A.

    2012-02-01

    In the present work the application of laser cleaning in the conservation of cultural assets is reviewed and some further developments on the interpretation of the associated laser-material interaction regimes are reported. Both the state of the art and new insights mainly focus on systematic approaches addressed to the solution of representative cleaning problems, including stone and metal artifacts along with wall and easel paintings. The innovative part is entirely dedicated to the extension of the application perspective of the Nd:YAG lasers by exploiting the significant versatility provided by their different pulse durations. Besides extensively discussing the specific conservation and physical problems involved in stone and metal cleaning, a significant effort was also made to explore the application potential for wall and easel paintings. The study of the latter was confined to preliminary irradiation tests carried out on prepared samples. We characterized the ablation phenomenology, optical properties, and photomechanical generation associated with the irradiation of optically absorbing varnishes using pulse durations of 10 and 120 ns. Further results concern the nature of the well-known problem of the yellowish appearance in stone cleaning, removal of biological growths and graffiti from stones, cleaning of bronze and iron artifacts and related aspects of laser conversion of unstable minerals, removal of calcareous stratification from wall paintings, and other features.

  15. 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...

  16. Mechanistic insights into ferredoxin-NADP(H) reductase catalysis involving the conserved glutamate in the active site.

    Science.gov (United States)

    Dumit, Verónica I; Essigke, Timm; Cortez, Néstor; Ullmann, G Matthias

    2010-04-02

    Plant-type ferredoxin-NADP(H) reductases (FNRs) are flavoenzymes harboring one molecule of noncovalently bound flavin adenine dinucleotide that catalyze reversible reactions between obligatory one-electron carriers and obligatory two-electron carriers. A glutamate next to the C-terminus is strictly conserved in FNR and has been proposed to function as proton donor/acceptor during catalysis. However, experimental studies of this proposed function led to contradicting conclusions about the role of this glutamate in the catalytic mechanism. In the present work, we study the titration behavior of the glutamate in the active site of FNR using theoretical methods. Protonation probabilities for maize FNR were computed for the reaction intermediates of the catalytic cycle by Poisson-Boltzmann electrostatic calculations and Metropolis Monte Carlo titration. The titration behavior of the highly conserved glutamate was found to vary depending on the bound substrates NADP(H) and ferredoxin and also on the redox states of these substrates and the flavin adenine dinucleotide. Our results support the involvement of the glutamate in the FNR catalytic mechanism not only as a proton donor but also as a key residue for stabilizing and destabilizing reaction intermediates. On the basis of our findings, we propose a model rationalizing the function of the glutamate in the reaction cycle, which allows reinterpretation of previous experimental results. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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.

  19. 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."

  20. 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

  1. Program activities, DOE state and local assistance programs, 1980 report

    Energy Technology Data Exchange (ETDEWEB)

    Chiogioji, Melvin H.

    1981-01-01

    Progress achieved by DOE State and Local Assistance Programs during FY 1980 and since they were established is summarized. These programs enable improved energy efficiency of industry, transportation, commercial establishments, public buildings, and residences. Eight programs (State Energy Conservation, Energy Extension Service, Weatherization Assistance, Institutional Buildings Grants, Energy-Related Inventions, Appropriate Technology Small Grants, Emergency Energy Conservation, Emergency Building Temperature Restrictions) are described. They provide the impetus for thousands of individual and organizational actions that have significantly affected national energy use patterns. (MCW)

  2. 34 CFR 300.812 - Reservation for State activities.

    Science.gov (United States)

    2010-07-01

    ... preceding fiscal year in the State's allocation under section 619 of the Act; or (2) The rate of inflation, as measured by the percentage increase, if any, from the preceding fiscal year in the Consumer Price Index for All Urban Consumers, published by the Bureau of Labor Statistics of the Department of Labor...

  3. 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.
    Gluc

  4. 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

  5. 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…

  6. 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,"…

  7. 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

  8. 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.

  9. 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...

  10. 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.

  11. 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...... during spontaneously varying sleep/waking states. Sequential state transitions from active waking to quiet waking, quiet sleep and active sleep were accompanied by progressively increased levels of PVH activity. Overall activity was highest during active sleep, and decreased markedly upon awakening...

  12. 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... report on its activities under the grant. The State Water Resources Research Institute Program issues an... Water Resources Research Act of 1984, as amended (42 U.S.C. 10301 et seq.), authorizes a water resources...

  13. 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 ...

  14. 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,…

  15. 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)...

  16. 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.

  17. 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.

  18. Safety insights from forensics evaluations at Daiichi

    Directory of Open Access Journals (Sweden)

    J. Rempe

    2017-01-01

    Information obtained from Daiichi is required to inform Decontamination and Decommissioning activities, improving the ability of the Tokyo Electric Power Company (TEPCO to characterize potential hazards and to ensure the safety of workers involved with cleanup activities. This paper reports initial results from the US Forensics Effort to utilize examination information obtained by TEPCO to enhance the safety of existing and future nuclear power plant designs. In this paper, three examples are presented in which examination information, such as visual images, dose surveys, sample evaluations, and muon tomography examinations, along with data from plant instrumentation, are used to obtain significant safety insights in the areas of component performance, fission product release and transport, debris end-state location, and combustible gas generation and transport. In addition to reducing uncertainties related to severe accident modeling progression, these insights confirm actions, such as the importance of water addition and containment venting, that are emphasized in updated guidance for severe accident prevention, mitigation, and emergency planning.

  19. 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.

  20. Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

    Science.gov (United States)

    Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

    2014-10-10

    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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Insights into Nano- and Micron-Scale Phase Separation in Amorphous Solid Dispersions Using Fluorescence-Based Techniques in Combination with Solid State Nuclear Magnetic Resonance Spectroscopy.

    Science.gov (United States)

    Purohit, Hitesh S; Ormes, James D; Saboo, Sugandha; Su, Yongchao; Lamm, Matthew S; Mann, Amanda K P; Taylor, Lynne S

    2017-07-01

    Miscibility between the drug and the polymer in an amorphous solid dispersion (ASD) is considered to be one of the most important factors impacting the solid state stability and dissolution performance of the active pharmaceutical ingredient (API). The research described herein utilizes emerging fluorescence-based methodologies to probe (im)miscibility of itraconazole (ITZ)-hydroxypropyl methylcellulose (HPMC) ASDs. The ASDs were prepared by solvent evaporation with varying evaporation rates and were characterized by steady-state fluorescence spectroscopy, confocal imaging, differential scanning calorimetry (DSC), and solid state nuclear magnetic resonance (ssNMR) spectroscopy. The size of the phase separated domains for the ITZ-HPMC ASDs was affected by the solvent evaporation rate. Smaller domains (30 nm) were found in ASDs prepared using slower evaporation rates. Confocal imaging provided visual confirmation of phase separation along with chemical specificity, achieved by selectively staining drug-rich and polymer-rich phases. ssNMR confirmed the results of fluorescence-based techniques and provided information on the size of phase separated domains. The fluorescence-based methodologies proved to be sensitive and rapid in detecting phase separation, even at the nanoscale, in the ITZ-HPMC ASDs. Fluorescence-based methods thus show promise for miscibility evaluation of spray-dried ASDs.

  11. 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.

  12. Neutron structure of the T26H mutant of T4 phage lysozyme provides insight into the catalytic activity of the mutant enzyme and how it differs from that of wild type.

    Science.gov (United States)

    Hiromoto, Takeshi; Meilleur, Flora; Shimizu, Rumi; Shibazaki, Chie; Adachi, Motoyasu; Tamada, Taro; Kuroki, Ryota

    2017-07-13

    T4 phage lysozyme is an inverting glycoside hydrolase that degrades the murein of bacterial cell walls by cleaving the β-1,4-glycosidic bond. The substitution of the catalytic Thr26 residue to a histidine converts the wild type from an inverting to a retaining enzyme, which implies that the original general acid Glu11 can also act as an acid/base catalyst in the hydrolysis. Here, we have determined the neutron structure of the perdeuterated T26H mutant to clarify the protonation states of Glu11 and the substituted His26, which are key in the retaining reaction. The 2.09-Å resolution structure shows that the imidazole group of His26 is in its singly protonated form in the active site, suggesting that the deprotonated Nɛ2 atom of His26 can attack the anomeric carbon of bound substrate as a nucleophile. The carboxyl group of Glu11 is partially protonated and interacts with the unusual neutral state of the guanidine moiety of Arg145, as well as two heavy water molecules. Considering that one of the water-binding sites has the potential to be occupied by a hydronium ion, the bulk solvent could be the source for the protonation of Glu11. The respective protonation states of Glu11 and His26 are consistent with the bond lengths determined by an unrestrained refinement of the high-resolution X-ray structure of T26H at 1.04-Å resolution. The detail structural information, including the coordinates of the deuterium atoms in the active site, provides insight into the distinctively different catalytic activities of the mutant and wild type enzymes. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  13. Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system.

    Science.gov (United States)

    Stefan, Loic; Denat, Franck; Monchaud, David

    2012-09-01

    Since the initial discovery of the catalytic capability of short DNA fragments, this peculiar enzyme-like property (termed DNAzyme) has continued to garner much interest in the scientific community because of the virtually unlimited applications in developing new molecular devices. Alongside the exponential rise in the number of DNAzyme applications in the last past years, the search for convenient ways to improve its overall efficiency has only started to emerge. Credence has been lent to this strategy by the recent demonstration that the quadruplex-based DNAzyme proficiency can be enhanced by ATP supplements. Herein, we have made a further leap along this path, trying first of all to decipher the actual DNAzyme catalytic cycle (to gain insights into the steps ATP may influence), and subsequently investigating in detail the influence of all the parameters that govern the catalytic efficiency. We have extended this study to other nucleotides and quadruplexes, thus demonstrating the versatility and broad applicability of such an approach. The defined exquisitely efficient DNAzyme protocols were exploited to highlight the enticing advantages of this method via a 96-well plate experiment that enables the detection of nanomolar DNA concentrations in real-time with the naked-eye (see movie as Supplementary Data).

  14. Qualitative insights into how men with low-risk prostate cancer choosing active surveillance negotiate stress and uncertainty.

    Science.gov (United States)

    Mader, Emily M; Li, Hsin H; Lyons, Kathleen D; Morley, Christopher P; Formica, Margaret K; Perrapato, Scott D; Irwin, Brian H; Seigne, John D; Hyams, Elias S; Mosher, Terry; Hegel, Mark T; Stewart, Telisa M

    2017-05-08

    Active surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach. Thematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance. The decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress. Support systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

  15. Activities on Facebook reveal the depressive state of users.

    Science.gov (United States)

    Park, Sungkyu; Lee, Sang Won; Kwak, Jinah; Cha, Meeyoung; Jeong, Bumseok

    2013-10-01

    As online social media have become prominent, much effort has been spent on identifying users with depressive symptoms in order to aim at early diagnosis, treatment, and even prevention by using various online social media. In this paper, we focused on Facebook to discern any correlations between the platform's features and users' depressive symptoms. This work may be helpful in trying to reach and detect large numbers of depressed individuals more easily. Our goal was to develop a Web application and identify depressive symptom-related features from users of Facebook, a popular social networking platform. 55 Facebook users (male=40, female=15, mean age 24.43, SD 3.90) were recruited through advertisement fliers distributed to students in a large university in Korea. Using EmotionDiary, the Facebook application we developed, we evaluated depressive symptoms using the Center for Epidemiological Studies-Depression (CES-D) scale. We also provided tips and facts about depression to participants and measured their responses using EmotionDiary. To identify the Facebook features related to depression, correlation analyses were performed between CES-D and participants' responses to tips and facts or Facebook social features. Last, we interviewed depressed participants (CES-D≥25) to assess their depressive symptoms by a psychiatrist. Facebook activities had predictive power in distinguishing depressed and nondepressed individuals. Participants' response to tips and facts, which can be explained by the number of app tips viewed and app points, had a positive correlation (P=.04 for both cases), whereas the number of friends and location tags had a negative correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in finding group differences in Facebook social activities, app tips viewed and app points resulted in significant differences (P=.01 and P=.03 respectively) between probably depressed and nondepressed individuals. Our results using Emotion

  16. 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.

  17. 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.

  18. 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

  19. Correlation between Cortical State and Locus Coeruleus Activity: Implications for Sensory Coding in Rat Barrel Cortex

    Directory of Open Access Journals (Sweden)

    Zeinab eFazlali

    2016-03-01

    Full Text Available Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory barrel cortex (BC. We simultaneously recorded unit activity from LC and BC along with prefrontal EEG while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100-400 ms post stimulus onset: almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios. These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state and the consequent

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Computational insights into active site shaping for substrate specificity and reaction regioselectivity in the EXTL2 retaining glycosyltransferase.

    Science.gov (United States)

    Mendoza, Fernanda; Lluch, José M; Masgrau, Laura

    2017-09-14

    Glycosyltransferases are enzymes that catalyze a monosaccharide transfer reaction from a donor to an acceptor substrate with the synthesis of a new glycosidic bond. They are highly substrate specific and regioselective, even though the acceptor substrate often presents multiple reactive groups. Currently, many efforts are dedicated to the development of biocatalysts for glycan synthesis and, therefore, a better understanding of how natural enzymes achieve this goal can be of valuable help. To gain a deeper insight into the catalytic strategies used by retaining glycosyltransferases, the wild type EXTL2 (CAZy family GT64) and four mutant forms (at positions 293 and 246) were studied using QM(DFT)/MM calculations and molecular dynamics simulations. Existing hypotheses on the roles of Arg293, an enigmatic residue in the CAZy family GT64 that seemed to contradict a mechanism through an oxocarbenium intermediate, and of Asp246 have been tested. We also provide a molecular interpretation for the results of site-directed mutagenesis experiments. Moreover, we have investigated why an Asp, and not a Glu like in the family GT6, is found on the β-face of the transferred GlcNAc. It is predicted that an Asp246Glu mutant of EXTL2 would be unable to catalyze the α-1,4 transfer. The results herein presented clarify the roles that Arg293, Asp246 and Leu213 have at different stages of the catalytic process (for binding but also for efficient chemical reaction). Altogether, we provide a molecular view that connects the identity and conformation of these residues to the substrate specificity and regioselectivity of the enzyme, illustrating a delicate interplay between all these aspects.

  5. 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.

  6. An insight into the effects of B-site transition metals on the activity, activation effect and stability of perovskite oxygen electrodes for solid oxide electrolysis cells

    Science.gov (United States)

    Bi, Jiaxin; Yang, Shengbing; Zhong, Shaohua; Wang, Jian-Qiang; Fan, Chou; Chen, Xinbing; Liu, Yihui

    2017-09-01

    Here, effects of B-site transition metals (TMs) in the (La0.6Sr0.4)XO3-δ (X = Mn, Fe, Co) perovskite structure on the activity and stability of the oxygen electrodes during high temperature electrolysis are discussed to provide a deep understanding of the phenomena observed for different oxygen electrodes under anodic polarizations. Performance and stability of the electrodes vary significantly at 800 °C as the TMs changed from Mn to Fe and Co, which is attributed to the different ionic conductivities and surface chemistry of the materials that have a strong dependence on the valence state and electronic structure of TMs. Under an anodic current passage of 200 mA cm-2 at 800 °C, electrode polarization resistance (RE) and overpotential (η) of the (La0.6Sr0.4)MnO3-δ (LSM) electrode decrease significantly by 1.75 Ω cm2 and 101 mV during the 1200 min test, compared with the constant values of RE and η for the (La0.6Sr0.4)FeO3-δ (LSF) and (La0.6Sr0.4)CoO3-δ (LSC) electrodes, an indication of the influence of B-site TMs on the electrode performance and stability. Most serious degradation is observed at the (La0.6Sr0.4)MnO3-δ electrode due to the electrode detachment arising from the accelerated SrO surface segregation and related disintegration of LSM particles near the electrode/electrolyte interface.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Mechanistic insight into conjugated N-N bond cleavage by Rh(III)-catalyzed redox-neutral C-H activation of pyrazolones.

    Science.gov (United States)

    Wu, Weirong; Liu, Yuxia; Bi, Siwei

    2015-08-14

    Density functional theory (DFT) calculations have been performed to investigate the detailed mechanism of Rh(III)-catalyzed redox-neutral C-H activation of pyrazolones with PhC≡CPh. It is found that (1) the methylene C-H activation is prior to the phenyl C-H activation, (2) the N-N bond cleavage is realized via Rh(III) → Rh(I) → Rh(III) rather than via Rh(III) → Rh(V) → Rh(III). The zwitterionic Rh(I) complex is identified to be a key intermediate in promoting the N-N bond cleavage. (3) Different from the Rh(III)-catalyzed hydrazine-directed C-H activation for indole synthesis, the rate-determining step of the reaction studied in this work is the Rh(III) → Rh(I) → Rh(III) process resulting in the N-N bond cleavage rather than the alkyne insertion step. The present theoretical study provides new insight into the mechanism of the conjugated N-N bond cleavage.

  15. 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

  16. 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…

  17. 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...

  18. Polyol accumulation by Aspergillus oryzae at low water activity in solid-state fermentation

    NARCIS (Netherlands)

    Ruijter, G.J.G.; Visser, J.; Rinzema, A.

    2004-01-01

    Polyol accumulation and metabolism were examined in Aspergillus oryzae cultured on whole wheat grains or on wheat dough as a model for solid-state culture. In solid-state fermentation (SSF), water activity (a(w)) is typically low resulting in osmotic stress. In addition to a high level of mannitol,

  19. 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... Water Resources (NIWR) USGS Competitive Grant Program. As required by the Paperwork Reduction Act (PRA... also find information about this ICR at www.reginfo.gov . SUPPLEMENTARY INFORMATION: Title: State Water...

  20. 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.

  1. 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. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Enhancing International Research and Development-Project Activity on University Campuses: Insights from U.S. Senior International Officers

    Science.gov (United States)

    Koehn, Peter H.; Deardorff, Darla K.; Bolognese, Kerry D.

    2011-01-01

    In the interconnected world of the UN Decade of Education for Sustainable Development, the ability of higher-education institutions to contribute to and benefit from international research undertakings, sustainable-development-project activity, and capacity-building endeavors requires transnational involvement. While the potential benefits are…

  3. 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.

  4. 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

  5. Using community insight to understand physical activity adoption in overweight and obese African American and Hispanic women: A qualitative study

    Science.gov (United States)

    Ecologic models suggest that multiple levels of influencing factors are important for determining physical activity participation and include individual, social, and environmental factors. The purpose of this qualitative study was to use an ecologic framework to gain a deeper understanding of the un...

  6. The importance of gradients in particle activity during sediment transport: Insights from a probabilistic description of particle motions

    Science.gov (United States)

    Furbish, D. J.

    2009-04-01

    Sediment particles transported by rainsplash, by bioturbation, and as bedload in turbulent flows, undergo motions that are quasi-random in magnitude and direction. Moreover, these motions characteristically are intermittent, in that particles are mostly at rest most of the time, and heterogeneous, in that the volumetric or areal concentration of particles in motion at any instant is spatially patchy. These particle motions can be formulated as a stochastic processes involving both advective and dispersive parts. By taking into account the intermittent activity of particles, and separating this activity from the physics of motion in the parametric description of transport, the formulation indicates that gradients in particle activity can have a key role in transport. The formulation illustrates, for example, how the growth of soil mounds beneath desert shrubs involves differential rainsplash that initially causes more grains to be splashed inward beneath protective shrub canopies than outward. This ‘harvesting' of nearby soil material, including nutrients, means that shrubs locally participate in regulating the rate sediment transport down a hillslope. With soil bioturbation, spatial variations in the disturbance frequency strongly influence the mixing of soil constituents, including distinct particle fractions (such as specific size or mineral fractions, seeds, or debitage), or elements and compounds adsorbed to particles. The formulation also provides a probabilistic version of the Exner equation. During bedload transport, gradients in particle activity, through both advective and dispersive effects, may contribute importantly to the local divergence of the particle flux, thereby influencing initial bedform growth.

  7. Insights into the mechanisms of Promysalin, a secondary metabolite with genus-specific antibacterial activity against Pseudomonas

    Science.gov (United States)

    Promysalin, a secondary metabolite produced by Pseudomonas putida RW10S1, has antibacterial activity against a wide variety of Pseudomonas sp., including both human and plant pathogens. Promysalin induces swarming and biofilm formation in the producing species, and inhibits growth of susceptible sp...

  8. 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.

  9. 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.

  10. 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.

  11. Cognitive insight: A systematic review.

    Science.gov (United States)

    Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

    2017-07-01

    Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

  12. 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.

  13. COP9-Signalosome deneddylase activity is enhanced by simultaneous neddylation: insights into the regulation of an enzymatic protein complex.

    Science.gov (United States)

    Bornstein, Gil; Grossman, Chagai

    2015-01-01

    Cullin-RING ubiquitin ligases (CRLs) are regulated by neddylation, which is a post translation modification of the Cullin family proteins. Neddylation of Cul1 activates the ligase through some means of biochemical mechanisms. The rate of neddylation and its extent are regulated by 2 opposing enzymatic processes: neddylation by an enzymatic cascade, and deneddylation by COP9-Signalosome (CSN) complex protein. The mechanism by which COP9-Signalosome catalytic activity is regulated is not well understood. We set an in vitro neddylation and deneddylation reaction using as a source for specific COP9/Signalosome deneddylase activity either Hela cells extract or purified Signalosome. Neddylation reaction of either endogenic Cul1 from Hela cells extract or recombinant Cul1 was catalyzed by recombinant neddylation enzymes. Deneddylation rate was tested either simultaneous to neddylation or after termination of neddylation by using an ATP depleting reaction or by directly inhibiting the neddylation activation enzyme named APP-BP1/UBA3 by its specific inhibitor MLN-4924. We demonstrated that neddylation and deneddylation are catalytically engaged and that inhibition of Cul1 neddylation significantly causes a decline in the rate of COP9-Signalosome deneddylase activity. Since neddylation is an ATP consuming reaction we managed to isolate the 2 opposing processes which surprisingly caused a decline in COP9 activity. Using MLN-4924 we demonstrated that direct inhibition of neddylation negatively influences the rate of deneddylation. The hypothesis that phosphorylation controls deneddylation was ruled out by the fact that no change in the rate of deneddylation was exemplified while converting the use of ATP with AMP-PNP. We demonstrated that deneddylation of Cul1 is positively regulated through direct simultaneous neddylation and is not dependent upon autophosphorylation. Defining the mechanism that regulates neddylation and deneddylation of Cullin proteins is important due to

  14. Understanding the main route of drug entry in adult Fasciola hepatica: Further insights into closantel pharmacological activity.

    Science.gov (United States)

    Ceballos, L; Canton, C; Cadenazzi, G; Larsen, K; Virkel, G; Moreno, L; Fairweather, I; Lanusse, C; Alvarez, L

    2017-10-01

    Closantel (CLS) is highly effective against adult liver flukes after its oral or subcutaneous (sc) administration in ruminants. Trans-tegumental diffusion and oral ingestion are the two potential routes available for the entry of drugs into Fasciola hepatica. The work reported here contributes to improve the understanding of CLS pharmacology. The main goals of were: I) to determine the pattern of in vivo CLS accumulation into adult F. hepatica and relevant tissues in CLS-treated sheep; II) to investigate the influence of the physicochemical composition of the incubation medium on the CLS diffusion process into adult F. hepatica; III) to assess the ovicidal activity of CLS against F. hepatica eggs; and IV) to investigate the in vivo effect of CLS treatment on glutathione S-transferases activity in adult liver flukes exposed to CLS. Fourteen healthy sheep were each orally infected with 75 F. hepatica metacercariae. Sixteen (16) weeks after infection, animals were treated with CLS by oral (n = 6, 10 mg/kg) or sub-cutaneous (sc) (n = 6, 5 mg/kg) route. At 12, 24 and 36 h post-treatment, animals were sacrificed (n = 2) and samples of blood, bile and adult F. hepatica were collected. In addition, flukes recovered from non-treated sheep (n = 2) were ex vivo incubated (60 min) in the presence of CLS in either RPMI or bile as incubation medium. CLS concentration was measured by HPLC. The ovicidal activity of CLS was investigated using eggs obtained from the bile of untreated sheep. Finally, glutathione S-transferase activity in F. hepatica recovered from untreated and CLS-treated sheep was assessed. In the in vivo studies, the highest CLS concentrations were measured in plasma and adult liver flukes. A positive correlation was observed between CLS concentration in plasma and in F. hepatica. Results obtained in the current work indicate that the in vivo accumulation of CLS into adult liver flukes occurs mainly by the oral route. After ex

  15. CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE: A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY.

    Science.gov (United States)

    Opmeer, Esther M; Kortekaas, Rudie; van Tol, Marie-José; Renken, Remco J; Demenescu, Liliana R; Woudstra, Saskia; Ter Horst, Gert J; van Buchem, Mark A; van der Wee, Nic J A; Veltman, Dick J; Aleman, André

    2016-01-01

    Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology. A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning. Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed. Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states. © 2015 Wiley Periodicals, Inc.

  16. 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.

  17. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. 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.

  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. Mechanism of Antibacterial Activity via Morphology Change of α-AgVO3: Theoretical and Experimental Insights.

    Science.gov (United States)

    de Oliveira, Regiane Cristina; de Foggi, Camila Cristina; Teixeira, Mayara Mondego; da Silva, Maya Dayana Penha; Assis, Marcelo; Francisco, Eric Mark; Pimentel, Bruna Natalia Alves da Silva; Pereira, Paula Fabiana Dos Santos; Vergani, Carlos Eduardo; Machado, Ana Lúcia; Andres, Juan; Gracia, Lourdes; Longo, Elson

    2017-04-05

    The electronic configuration, morphology, optical features, and antibacterial activity of metastable α-AgVO3 crystals have been discussed by a conciliation and association of the results acquired by experimental procedures and first-principles calculations. The α-AgVO3 powders were synthesized using a coprecipitation method at 10, 20, and 30 °C. By using a Wulff construction for all relevant low-index surfaces [(100), (010), (001), (110), (011), (101), and (111)], the fine-tuning of the desired morphologies can be achieved by controlling the values of the surface energies, thereby lending a microscopic understanding to the experimental results. The as-synthesized α-AgVO3 crystals display a high antibacterial activity against methicillin-resistant Staphylococcus aureus. The results obtained from the experimental and theoretical techniques allow us to propose a mechanism for understanding the relationship between the morphological changes and antimicrobial performance of α-AgVO3.

  1. Menadione Suppresses Benzo(α)pyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism.

    Science.gov (United States)

    Sidorova, Yulia A; Perepechaeva, Maria L; Pivovarova, Elena N; Markel, Arkady L; Lyakhovich, Vyacheslav V; Grishanova, Alevtina Y

    2016-01-01

    Oxidative reactions that are catalyzed by cytochromes P450 1A (CYP1A) lead to formation of carcinogenic derivatives of arylamines and polycyclic aromatic hydrocarbons (PAHs), such as the widespread environmental pollutant benzo(α)pyrene (BP). These compounds upregulate CYP1A at the transcriptional level via an arylhydrocarbon receptor (AhR)-dependent signaling pathway. Because of the involvement of AhR-dependent genes in chemically induced carcinogenesis, suppression of this signaling pathway could prevent tumor formation and/or progression. Here we show that menadione (a water-soluble analog of vitamin K3) inhibits BP-induced expression and enzymatic activity of both CYP1A1 and CYP1A2 in vivo (in the rat liver) and BP-induced activity of CYP1A1 in vitro. Coadministration of BP and menadione reduced DNA-binding activity of AhR and increased DNA-binding activity of transcription factors Oct-1 and CCAAT/enhancer binding protein (C/EBP), which are known to be involved in negative regulation of AhR-dependent genes, in vivo. Expression of another factor involved in downregulation of CYP1A-pAhR repressor (AhRR)-was lower in the liver of the rats treated with BP and menadione, indicating that the inhibitory effect of menadione on CYP1A is not mediated by this protein. Furthermore, menadione was well tolerated by the animals: no signs of acute toxicity were detected by visual examination or by assessment of weight gain dynamics or liver function. Taken together, our results suggest that menadione can be used in further studies on animal models of chemically induced carcinogenesis because menadione may suppress tumor formation and possibly progression.

  2. Menadione Suppresses Benzo(αpyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism.

    Directory of Open Access Journals (Sweden)

    Yulia A Sidorova

    Full Text Available Oxidative reactions that are catalyzed by cytochromes P450 1A (CYP1A lead to formation of carcinogenic derivatives of arylamines and polycyclic aromatic hydrocarbons (PAHs, such as the widespread environmental pollutant benzo(αpyrene (BP. These compounds upregulate CYP1A at the transcriptional level via an arylhydrocarbon receptor (AhR-dependent signaling pathway. Because of the involvement of AhR-dependent genes in chemically induced carcinogenesis, suppression of this signaling pathway could prevent tumor formation and/or progression. Here we show that menadione (a water-soluble analog of vitamin K3 inhibits BP-induced expression and enzymatic activity of both CYP1A1 and CYP1A2 in vivo (in the rat liver and BP-induced activity of CYP1A1 in vitro. Coadministration of BP and menadione reduced DNA-binding activity of AhR and increased DNA-binding activity of transcription factors Oct-1 and CCAAT/enhancer binding protein (C/EBP, which are known to be involved in negative regulation of AhR-dependent genes, in vivo. Expression of another factor involved in downregulation of CYP1A-pAhR repressor (AhRR-was lower in the liver of the rats treated with BP and menadione, indicating that the inhibitory effect of menadione on CYP1A is not mediated by this protein. Furthermore, menadione was well tolerated by the animals: no signs of acute toxicity were detected by visual examination or by assessment of weight gain dynamics or liver function. Taken together, our results suggest that menadione can be used in further studies on animal models of chemically induced carcinogenesis because menadione may suppress tumor formation and possibly progression.

  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. 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...

  5. 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.

  6. 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. ...

  7. Vulnerability of the Nigerian coast: An insight into sea level rise owing to climate change and anthropogenic activities

    Science.gov (United States)

    Danladi, Iliya Bauchi; Kore, Basiru Mohammed; Gül, Murat

    2017-10-01

    Coastal areas are important regions in the world as they host huge population, diverse ecosystems and natural resources. However, owing to their settings, elevations and proximities to the sea, climate change (global warming) and human activities are threatening issues. Herein, we report the coastline changes and possible future threats related to sea level rise owing to global warming and human activities in the coastal region of Nigeria. Google earth images, Digital Elevation Model (DEM) and geological maps were used. Using google earth images, coastal changes for the past 43 years, 3 years prior to and after the construction of breakwaters along Goshen Beach Estate (Lekki) were examined. Additionally, coastline changes along Lekki Phase I from 2013 to 2016 were evaluated. The DEM map was used to delineate 0-2 m, 2-5 m and 5-10 m asl which correspond to undifferentiated sands and gravels to clays on the geological map. The results of the google earth images revealed remarkable erosion along both Lekki and Lekki Phase I, with the destruction of a lagoon in Lekki Phase I. Based on the result of the DEM map and geology, elevations of 0-2 m, 2-5 m and 5-10 m asl were interpreted as highly risky, moderately risky and risky respectively. Considering factors threatening coastal regions, the erosion and destruction of the lagoon along the Nigerian coast may be ascribed to sea level rise as a result of global warming and intense human activities respectively.

  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. New Insights in Thrombin Inhibition Structure–Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin

    Directory of Open Access Journals (Sweden)

    Pierre A. J. Mourier

    2017-03-01

    Full Text Available Low Molecular Weight Heparins (LMWH are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin. However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity.

  10. 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.

  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. 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

  13. 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.

  14. 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.

  15. Decreased activation of subcortical brain areas in the motor fatigue state: an fMRI study

    Directory of Open Access Journals (Sweden)

    Lijuan Hou

    2016-08-01

    Full Text Available One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e. thalamus and basal ganglia areas are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state.

  16. Natural Environments, Obesity, and Physical Activity in Nonmetropolitan Areas of the United States

    Science.gov (United States)

    Michimi, Akihiko; Wimberly, Michael C.

    2012-01-01

    Purpose: To assess the associations of the natural environment with obesity and physical activity in nonmetropolitan areas of the United States among representative samples by using 2 indices of outdoor activity potential (OAP) at the county level. Methods: We used the data from 457,820 and 473,296 noninstitutionalized adults aged over 18 years…

  17. Active zone impact on deformation state of non-rigid pavement

    Science.gov (United States)

    Mandula, Ján

    2014-06-01

    The paper deals with the design of non-rigid pavement, with emphasis on the effect of active zone on its deformation state. The concepts of determination of active zone are described. The results of numerical modelling of pavement laying on elastic subgrade are presented in the paper

  18. Active zone impact on deformation state of non-rigid pavement

    Directory of Open Access Journals (Sweden)

    Mandula Ján

    2014-06-01

    Full Text Available The paper deals with the design of non-rigid pavement, with emphasis on the effect of active zone on its deformation state. The concepts of determination of active zone are described. The results of numerical modelling of pavement laying on elastic subgrade are presented in the paper

  19. 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.

  20. Crystal-chemistry insight into the photocatalytic activity of BiOCl x Br1- x nanoplate solid solutions

    Science.gov (United States)

    Xu, Huan-Yan; Han, Xu; Tan, Qu; Wu, Ke-Jia; Qi, Shu-Yan

    2017-06-01

    In this study, a facile alcoholysis method was developed to synthesize BiOCl x Br1- x nanoplates at room temperature and atmospheric pressure. In this route, strong acid or alkaline environment was absolutely avoided to realize the high exposure of {001} crystal facets. The regular changes in XRD peaks and cell parameters as a function of the Br content strongly declared that the obtained BiOCl x Br1- x products belonged to a group of solid solutions. The 2D nanosheets with in-plane wrinkles were clearly observed in TEM images. Interestingly, as the Br content increased, band gaps of BiOCl x Br1- x solid solutions gradually decreased. The photocatalytic degradation of RhB under simulated sunlight irradiation indicated that BiOCl0.5Br0.5 had the best photocatalytic activity. From the viewpoint of crystal chemistry, the photocatalytic activity of BiOCl x Br1- x solid solutions was closely related with the exposure amount of {001} facets, interlayer spacing of (001) plane and energy-level position of valence band.

  1. Co,N-codoped graphene as efficient electrocatalyst for hydrogen evolution reaction: Insight into the active centre

    Science.gov (United States)

    Wang, Shumin; Zhang, Lei; Qin, Yong; Ding, Dong; Bu, Yunfei; Chu, Fuqiang; Kong, Yong; Liu, Meilin

    2017-09-01

    Co and N co-doped carbon (CNC) material is one of the most promising precious-metal-free catalyst for hydrogen evolution reaction (HER), however, widespread application of CNC will require continuous innovation and optimization of fabrication to maximize electrocatalytic performance, which is always a challenge. Herein, two types of three-dimensional (3D) graphene materials synthesized by one-step of simultaneous doping (Co,N/3DG-1) and two-step of sequential doping (Co,N/3DG-2) respectively, are evaluated and correlated their electrocatalytic activity for HER with experimental parameters. The results indicate that Co,N/3DG-2 exhibits significantly better electrocatalytic activity than Co,N/3DG-1. The structure analysis reveals that Co,N/3DG-2 has more moderate Co-N coordinated number than Co,N/3DG-1. Density functional theory calculations unravels that the equilibrium C and N around Co atom is more favorable to the adsorption and desorption of hydrogen. The results shed new light on the rational design of dual hetero-atom co-doped carbon materials, which may be applicable to other energy conversion and storage systems.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Bhalla, Amneet Pal Singh; Griffith, Boyce E; Patankar, Neelesh A

    2013-01-01

    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.

  5. Direct atomic-level insight into the active sites of a high-performance PGM-free ORR catalyst

    Science.gov (United States)

    Chung, Hoon T.; Cullen, David A.; Higgins, Drew; Sneed, Brian T.; Holby, Edward F.; More, Karren L.; Zelenay, Piotr

    2017-08-01

    Platinum group metal-free (PGM-free) metal-nitrogen-carbon catalysts have emerged as a promising alternative to their costly platinum (Pt)-based counterparts in polymer electrolyte fuel cells (PEFCs) but still face some major challenges, including (i) the identification of the most relevant catalytic site for the oxygen reduction reaction (ORR) and (ii) demonstration of competitive PEFC performance under automotive-application conditions in the hydrogen (H2)-air fuel cell. Herein, we demonstrate H2-air performance gains achieved with an iron-nitrogen-carbon catalyst synthesized with two nitrogen precursors that developed hierarchical porosity. Current densities recorded in the kinetic region of cathode operation, at fuel cell voltages greater than ~0.75 V, were the same as those obtained with a Pt cathode at a loading of 0.1 milligram of Pt per centimeter squared. The proposed catalytic active site, carbon-embedded nitrogen-coordinated iron (FeN4), was directly visualized with aberration-corrected scanning transmission electron microscopy, and the contributions of these active sites associated with specific lattice-level carbon structures were explored computationally.

  6. NTB-A Receptor Crystal Structure: Insights into Homophilic Interactions in the Signaling Lymphocytic Activation Molecule Receptor Family

    Energy Technology Data Exchange (ETDEWEB)

    Cao,E.; Ramagopal, U.; Fedorov, A.; Fedorov, E.; Yan, Q.; Lary, J.; Cole, J.; Nathenson, S.; Almo, S.

    2006-01-01

    The signaling lymphocytic activation molecule (SLAM) family includes homophilic and heterophilic receptors that regulate both innate and adaptive immunity. The ectodomains of most SLAM family members are composed of an N-terminal IgV domain and a C-terminal IgC2 domain. NK-T-B-antigen (NTB-A) is a homophilic receptor that stimulates cytotoxicity in natural killer (NK) cells, regulates bactericidal activities in neutrophils, and potentiates T helper 2 (Th2) responses. The 3.0 {angstrom} crystal structure of the complete NTB-A ectodomain revealed a rod-like monomer that self-associates to form a highly kinked dimer spanning an end-to-end distance of {approx}100 {angstrom}. The NTB-A homophilic and CD2-CD58 heterophilic dimers show overall structural similarities but differ in detailed organization and physicochemical properties of their respective interfaces. The NTB-A structure suggests a mechanism responsible for binding specificity within the SLAM family and imposes physical constraints relevant to the colocalization of SLAM-family proteins with other signaling molecules in the immunological synapse.

  7. 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.

  8. 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.

  9. 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.

  10. Cloud droplet activation through oxidation of organic aerosol influenced by temperature and particle phase state

    Science.gov (United States)

    Slade, Jonathan H.; Shiraiwa, Manabu; Arangio, Andrea; Su, Hang; Pöschl, Ulrich; Wang, Jian; Knopf, Daniel A.

    2017-02-01

    Chemical aging of organic aerosol (OA) through multiphase oxidation reactions can alter their cloud condensation nuclei (CCN) activity and hygroscopicity. However, the oxidation kinetics and OA reactivity depend strongly on the particle phase state, potentially influencing the hydrophobic-to-hydrophilic conversion rate of carbonaceous aerosol. Here, amorphous Suwannee River fulvic acid (SRFA) aerosol particles, a surrogate humic-like substance (HULIS) that contributes substantially to global OA mass, are oxidized by OH radicals at different temperatures and phase states. When oxidized at low temperature in a glassy solid state, the hygroscopicity of SRFA particles increased by almost a factor of two, whereas oxidation of liquid-like SRFA particles at higher temperatures did not affect CCN activity. Low-temperature oxidation appears to promote the formation of highly-oxygenated particle-bound fragmentation products with lower molar mass and greater CCN activity, underscoring the importance of chemical aging in the free troposphere and its influence on the CCN activity of OA.

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Forearc oceanic crust in the Izu-Bonin arc - new insights from active-source seismic survey -

    Science.gov (United States)

    Kodaira, S.; Noguchi, N.; Takahashi, N.; Ishizuka, O.; Kaneda, Y.

    2009-12-01

    Petrological studies have suggested that oceanic crust is formed in forearc areas during the initial stage of subduction. However, there is little geophysical evidence for the formation of oceanic crust in those regions. In order to examine crustal formation process associated with a subduction initiation process, we conducted an active-source seismic survey at a forearc region in the Izu-Bonin intra-oceanic arc. The resultant seismic image shows a remarkably thin crust (less than 10 km) at the northern half of the Bonin ridge (at the north of the Chichi-jima) and abrupt thickening the crust (~ 20 km thick) toward the south (at the Haha-jima). Comparison of velocity-depth profiles of the thin forearc crust of the Bonin ridge with those of typical oceanic crusts showed them to be seismologically identical. The observed structural variation also well corresponds to magmatic activities along the forearc. Boninitic magmatism is evident in the area of thin crust and tholeiitic-calcalkaline andesitic volcanism in the area of thick crust. Based on high precision dating studies of those volcanic rocks, we interpreted that the oceanic-type thin crust associated with boninitic volcanism has been created soon after the initiation of subduction (45-48 Ma) and and that the nonoceanic thick crust was created by tholeiitic-calcalkaline andesitic magmatism after the boninitic magmatism was ceased. The above seismological evidences strongly support the idea of forearc oceanic crust (or phiolite) created by forearc spreading in the initial stage of subduction along the intra-oceanic arc.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Activity and relationships of muscular and cardiovascular systems in different states during muscular activity in athletes.

    Directory of Open Access Journals (Sweden)

    Pryimakov A.A.

    2012-11-01

    Full Text Available Revealed that the performance of high-power exercise on a bicycle ergometer to failure athletes skilled cyclists (15 men increases the activity and relationship of muscular and cardiovascular systems. At rest and fatigue manifests linear relationship between the two systems, during commissioning with stable condition - is exponential. The development of fatigue compensated without changing leadership of the quadriceps, biceps and calf muscles of the lower extremities in the efforts to change the relationship and partial role in various areas of cyclic motion, increasing their electrical activity. With the development of decompensated fatigue decreases the electrical activity and disturbed coordination of major muscles in the relationship right and left limbs.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Tian, Ye; Tan, Yanglan; Liu, Na; Yan, Zheng; Liao, Yucai; Chen, Jie; de Saeger, Sarah; Yang, Hua; Zhang, Qiaoyan; Wu, Aibo

    2016-01-01

    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. PMID:27854265

  10. New insight into adsorption characteristics and mechanisms of the biosorbent from waste activated sludge for heavy metals.

    Science.gov (United States)

    Zhou, Yun; Zhang, Zhiqiang; Zhang, Jiao; Xia, Siqing

    2016-07-01

    The adsorption characteristics and mechanisms of the biosorbent from waste activated sludge were investigated by adsorbing Pb(2+) and Zn(2+) in aqueous single-metal solutions. A pH value of the metal solutions at 6.0 was beneficial to the high adsorption quantity of the biosorbent. The optimal mass ratio of the biosorbent to metal ions was found to be 2. A higher adsorption quantity of the biosorbent was achieved by keeping the reaction temperature below 55°C. Response surface methodology was applied to optimize the biosorption processes, and the developed mathematical equations showed high determination coefficients (above 0.99 for both metal ions) and insignificant lack of fit (p=0.0838 and 0.0782 for Pb(2+) and Zn(2+), respectively). Atomic force microscopy analyses suggested that the metal elements were adsorbed onto the biosorbent surface via electrostatic interaction. X-ray photoelectron spectroscopy analyses indicated the presence of complexation (between -NH2, -CN and metal ions) and ion-exchange (between -COOH and metal ions). The adsorption mechanisms could be the combined action of electrostatic interaction, complexation and ion-exchange between functional groups and metal ions. Copyright © 2016. Published by Elsevier B.V.

  11. 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.

  12. A Forced Damped Oscillation Framework for Undulatory Swimming Provides New Insights into How Propulsion Arises in Active and Passive Swimming

    Science.gov (United States)

    Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Patankar, Neelesh A.

    2013-01-01

    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. PMID:23785272

  13. New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

    Science.gov (United States)

    Neher, Miriam D.; Weckbach, Sebastian; Huber-Lang, Markus S.; Stahel, Philip F.

    2012-01-01

    Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed. PMID:22481914

  14. 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

  15. Insight into mechanisms of 3′-5′ exonuclease activity and removal of bulky 8,5′-cyclopurine adducts by apurinic/apyrimidinic endonucleases

    Science.gov (United States)

    Mazouzi, Abdelghani; Vigouroux, Armelle; Aikeshev, Bulat; Brooks, Philip J.; Saparbaev, Murat K.; Morera, Solange; Ishchenko, Alexander A.

    2013-01-01

    8,5′-cyclo-2'-deoxyadenosine (cdA) and 8,5′-cyclo-2'-deoxyguanosine generated in DNA by both endogenous oxidative stress and ionizing radiation are helix-distorting lesions and strong blocks for DNA replication and transcription. In duplex DNA, these lesions are repaired in the nucleotide excision repair (NER) pathway. However, lesions at DNA strand breaks are most likely poor substrates for NER. Here we report that the apurinic/apyrimidinic (AP) endonucleases—Escherichia coli Xth and human APE1—can remove 5′S cdA (S-cdA) at 3′ termini of duplex DNA. In contrast, E. coli Nfo and yeast Apn1 are unable to carry out this reaction. None of these enzymes can remove S-cdA adduct located at 1 or more nt away from the 3′ end. To understand the structural basis of 3′ repair activity, we determined a high-resolution crystal structure of E. coli Nfo-H69A mutant bound to a duplex DNA containing an α-anomeric 2′-deoxyadenosine:T base pair. Surprisingly, the structure reveals a bound nucleotide incision repair (NIR) product with an abortive 3′-terminal dC close to the scissile position in the enzyme active site, providing insight into the mechanism for Nfo-catalyzed 3′→5′ exonuclease function and its inhibition by 3′-terminal S-cdA residue. This structure was used as a template to model 3′-terminal residues in the APE1 active site and to explain biochemical data on APE1-catalyzed 3′ repair activities. We propose that Xth and APE1 may act as a complementary repair pathway to NER to remove S-cdA adducts from 3′ DNA termini in E. coli and human cells, respectively. PMID:23898172

  16. Insight into mechanisms of 3'-5' exonuclease activity and removal of bulky 8,5'-cyclopurine adducts by apurinic/apyrimidinic endonucleases.

    Science.gov (United States)

    Mazouzi, Abdelghani; Vigouroux, Armelle; Aikeshev, Bulat; Brooks, Philip J; Saparbaev, Murat K; Morera, Solange; Ishchenko, Alexander A

    2013-08-13

    8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine generated in DNA by both endogenous oxidative stress and ionizing radiation are helix-distorting lesions and strong blocks for DNA replication and transcription. In duplex DNA, these lesions are repaired in the nucleotide excision repair (NER) pathway. However, lesions at DNA strand breaks are most likely poor substrates for NER. Here we report that the apurinic/apyrimidinic (AP) endonucleases--Escherichia coli Xth and human APE1--can remove 5'S cdA (S-cdA) at 3' termini of duplex DNA. In contrast, E. coli Nfo and yeast Apn1 are unable to carry out this reaction. None of these enzymes can remove S-cdA adduct located at 1 or more nt away from the 3' end. To understand the structural basis of 3' repair activity, we determined a high-resolution crystal structure of E. coli Nfo-H69A mutant bound to a duplex DNA containing an α-anomeric 2'-deoxyadenosine:T base pair. Surprisingly, the structure reveals a bound nucleotide incision repair (NIR) product with an abortive 3'-terminal dC close to the scissile position in the enzyme active site, providing insight into the mechanism for Nfo-catalyzed 3'→5' exonuclease function and its inhibition by 3'-terminal S-cdA residue. This structure was used as a template to model 3'-terminal residues in the APE1 active site and to explain biochemical data on APE1-catalyzed 3' repair activities. We propose that Xth and APE1 may act as a complementary repair pathway to NER to remove S-cdA adducts from 3' DNA termini in E. coli and human cells, respectively.

  17. 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.

  18. 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.

  19. Active absorption of acoustic wave using state-space control approach

    Science.gov (United States)

    Wu, Zhen; Varadan, Vijay K.; Varadan, Vasundara V.; Lee, Kwang Y.

    1994-05-01

    This paper presents a computer modeling and simulation of an active sound absorbing system with an optimal state-feedback controller. First, a state-space model is developed to describe one-dimensional sound reflection and transmission in the time domain. In the model derivation, the difficulty of discretizing the wave equation in an unbounded region is overcome by combining the finite-difference and analytical solutions. Numerical simulation of the open- loop model response is performed, which shows a good agreement with the well known frequency domain solutions. Second, a state-feedback controller including a linear quadratic regulator and a Kalman filter type state-estimator is designed using the optimal control theory. Numerical simulation of the closed-loop model response of an active sound control system containing two sensors and one actuator is presented. It is shown that a broadband attenuation of more than 30 dB over 2 octaves has been reached.

  20. 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 ...

  1. Solid State Inflation Balloon Active Deorbiter: Scalable Low-Cost Deorbit System for Small Satellites

    Science.gov (United States)

    Huang, Adam

    2016-01-01

    The goal of the Solid State Inflation Balloon Active Deorbiter project is to develop and demonstrate a scalable, simple, reliable, and low-cost active deorbiting system capable of controlling the downrange point of impact for the full-range of small satellites from 1 kg to 180 kg. The key enabling technology being developed is the Solid State Gas Generator (SSGG) chip, generating pure nitrogen gas from sodium azide (NaN3) micro-crystals. Coupled with a metalized nonelastic drag balloon, the complete Solid State Inflation Balloon (SSIB) system is capable of repeated inflation/deflation cycles. The SSGG minimizes size, weight, electrical power, and cost when compared to the current state of the art.

  2. 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

  3. 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

  4. Cortical activation during clock reading as a quadratic function of dementia state.

    Science.gov (United States)

    Saur, Ralf; Milian, Monika; Erb, Michael; Eschweiler, Gerhard W; Grodd, Wolfgang; Leyhe, Thomas

    2010-01-01

    In patients with Alzheimer's disease (AD), neuroimaging studies have demonstrated decreased brain activation, while increased activation was detected in patients with mild cognitive impairment (MCI). It can be hypothesized that increased cerebral activity seen in patients with MCI reflects neural compensation at the beginning of neurodegenerative processes. Later, as patients develop AD, neural integrity is increasingly impaired. This is accompanied by decreased neural activation. In this study we examined cognitive performance and functional magnetic resonance imaging activation on a Clock Reading task (CRT) and a Spatial Control task (SCT) in healthy controls, patients with MCI, and patients with early AD. Correlations between neural-functional activation and cognitive state, measured by the Mini Mental Status Examination, were determined using rank, linear and quadratic correlation models. It could be shown that CRT, in comparison to SCT, specifically activates brain regions in the ventral visual stream and precuneus known to be involved in conceptual processing and spatial imagery. The correlation between brain activity and cognitive state followed a quadratic rather than a linear pattern in several brain regions, including the lingual gyrus, cuneus, and precuneus. The strongest brain activity was found in patients with MCI and less severely impaired early AD subjects. These findings support the hypothesis that patients in early stages of dementia compensate for neuronal loss by the recruitment of additional neural resources reflected by increased neural activation, as measured by the blood oxygen level-dependent signal.

  5. [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.

  6. Activity and recovery profiles of state-of-origin and national rugby league match-play.

    Science.gov (United States)

    Gabbett, Tim J

    2015-03-01

    State-of-Origin is the highest standard of rugby league competition played anywhere in the world. This study investigated the activity profiles of State-of-Origin and compared them against regular National Rugby League (NRL) fixture matches. Video footage from State-of-Origin and NRL matches were coded for activity and recovery cycles. Time when the ball was continuously in play was considered activity, whereas any stoppages during matches were considered recovery. Ball-in-play periods in matches of different playing standards were analyzed by comparing State-of-Origin matches, NRL matches (with representative players available), and NRL matches (with representative players unavailable). The mean, maximum, and total ball-in-play time of State-of-Origin matches were longer than NRL matches (effect size [ES] ≥ 0.75) with and without the availability of representative players. State-of-Origin matches were associated with a greater proportion (ES ≥ 1.54) of long duration (46-300 seconds) ball-in-play periods, and a smaller proportion (ES ≥ 1.69) of short duration (rugby league players to perform prolonged passages of high-intensity exercise during match-play.

  7. 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.

  8. 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.

  9. 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.

  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. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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…

  10. 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...

  11. 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...

  12. 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…

  13. 76 FR 44904 - Agency Information Collection Activities; Proposed Collection; Comment Request; State Water...

    Science.gov (U