WorldWideScience

Sample records for allosteric hot spots

  1. Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

    Science.gov (United States)

    Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

    2014-07-18

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs.

  2. Coulomb explosion of "hot spot"

    CERN Document Server

    Oreshkin, V I; Chaikovsky, S A; Artyomov, A P

    2016-01-01

    The study presented in this paper has shown that the generation of hard x rays and high-energy ions, which are detected in pinch implosion experiments, may be associated with the Coulomb explosion of the hot spot that is formed due to the outflow of the material from the pinch cross point. During the process of material outflow, the temperature of the hot spot plasma increases, and conditions arise for the plasma electrons to become continuously accelerated. The runaway of electrons from the hot spot region results in the buildup of positive space charge in this region followed by a Coulomb explosion. The conditions for the hot spot plasma electrons to become continuously accelerated have been revealed and estimates have been obtained for the kinetic energy of the ions generated by the Coulomb explosion.

  3. ESA uncovers Geminga's `hot spot'

    Science.gov (United States)

    2004-07-01

    16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of

  4. Computational Prediction of Hot Spot Residues

    OpenAIRE

    Morrow, John Kenneth; Zhang, Shuxing

    2012-01-01

    Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has pr...

  5. Hot spots of mutualistic networks.

    Science.gov (United States)

    Gilarranz, Luis J; Sabatino, Malena; Aizen, Marcelo A; Bascompte, Jordi

    2015-03-01

    Incorporating interactions into a biogeographical framework may serve to understand how interactions and the services they provide are distributed in space. We begin by simulating the spatiotemporal dynamics of realistic mutualistic networks inhabiting spatial networks of habitat patches. We proceed by comparing the predicted patterns with the empirical results of a set of pollination networks in isolated hills of the Argentinian Pampas. We first find that one needs to sample up to five times as much area to record interactions as would be needed to sample the same proportion of species. Secondly, we find that peripheral patches have fewer interactions and harbour less nested networks - therefore potentially less resilient communities - compared to central patches. Our results highlight the important role played by the structure of dispersal routes on the spatial distribution of community patterns. This may help to understand the formation of biodiversity hot spots. PMID:25402941

  6. Hot Spot Removal System: System description

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  7. Hot Spot Removal System: System description

    International Nuclear Information System (INIS)

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System''s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section

  8. HotSpot Software Configuration Management Plan

    Energy Technology Data Exchange (ETDEWEB)

    Walker, H; Homann, S G

    2009-03-12

    This Software Configuration Management Plan (SCMP) describes the software configuration management procedures used to ensure that the HotSpot dispersion model meets the requirements of its user base, which includes: (1) Users of the PC version of HotSpot for consequence assessment, hazard assessment and safety analysis calculations; and (2) Users of the NARAC Web and iClient software tools, which allow users to run HotSpot for consequence assessment modeling These users and sponsors of the HotSpot software and the organizations they represent constitute the intended audience for this document. This plan is intended to meet Critical Recommendations 1 and 3 from the Software Evaluation of HotSpot and DOE Safety Software Toolbox Recommendation for inclusion of HotSpot in the Department of Energy (DOE) Safety Software Toolbox. HotSpot software is maintained for the Department of Energy Office of Emergency Operations by the National Atmospheric Release Advisory Center (NARAC) at Lawrence Livermore National Laboratory (LLNL). An overview of HotSpot and NARAC are provided.

  9. Hot spots in fiber pinches

    International Nuclear Information System (INIS)

    Results are presented on the behavior of ''bright spots'' in carbon and deuterium fiber Z-pinches using the MAGPIE generator at the I MA current level. The experimental diagnosis was carried out using optical and X-ray framing and streak images, along with Schlieren and shadowgraphy laser probing. After a short (∼4 ns) duration formation phase, these bright spots exhibit highly dynamic behavior. Bifurcation of the bright spots gives rise to rapid axial motion at 1-3x105 m/sec. The post-bifurcation bright spots persist for up to 40 ns. The important features of bright spot evolution can be reproduced using a 2-D MHD code incorporating LTE ionization dynamics and cold start conditions. Construction of ''artificial'' diagnostic images from the simulation data allows direct comparison to experiment. From the close agreement between experiment and 2-D simulation we infer that the observed bright spot behavior can be explained entirely in terms of the non-linear evolution of the m=0 instability

  10. Statistical Hot Spot Model for Explosive Detonation

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, III, A L

    2005-07-14

    The Non-local Thermodynamic Equilibrium Statistical Hot Spot Model (NLTE SHS), a new model for explosive detonation, is described. In this model, the formation, ignition, propagation, and extinction of hot spots is explicitly modeled. The equation of state of the explosive mixture is treated with a non-local equilibrium thermodynamic assumption. A methodology for developing the parameters for the model is discussed, and applied to the detonation velocity diameter effect. Examination of these results indicates where future improvements to the model can be made.

  11. Statistical Hot Spot Model for Explosive Detonation

    Energy Technology Data Exchange (ETDEWEB)

    Nichols III, A L

    2004-05-10

    The Non-local Thermodynamic Equilibrium Statistical Hot Spot Model (NLTE SHS), a new model for explosive detonation, is described. In this model, the formation, ignition, propagation, and extinction of hot spots is explicitly modeled. The equation of state of the explosive mixture is treated with a nonlocal equilibrium thermodynamic assumption. A methodology for developing the parameters for the model is discussed, and applied to the detonation velocity diameter effect. Examination of these results indicates where future improvements to the model can be made.

  12. Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

    Energy Technology Data Exchange (ETDEWEB)

    Buhrman, Greg; O; #8242; Connor, Casey; Zerbe, Brandon; Kearney, Bradley M.; Napoleon, Raeanne; Kovrigina, Elizaveta A.; Vajda, Sandor; Kozakov, Dima; Kovrigin, Evgenii L.; Mattos, Carla (NCSU); (MCW); (BU)

    2012-09-17

    We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the 'off' and 'on' allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.

  13. Research Hot Spots of Black Peanut

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Taking the research papers on black peanut in National Knowledge Infrastructure(CNKI)as data sources,we determine the research hot spots on black peanut using word frequency analysis,and analyze the main research directions that change over the years.The results show that the relevant researches on black peanut are mainly concentrated in six themes(study of varieties,physiological property,cultivation management,development prospects,relationship with agriculture,and molecular level);varieties,physiology,cultivation and other aspects are the focus of current research hot spots;the researches on selection and breeding of variety and various physiological and ecological mechanisms,still need a breakthrough.

  14. Amorphous-silicon module hot-spot testing

    Science.gov (United States)

    Gonzalez, C. C.

    1985-01-01

    Hot spot heating occurs when cell short-circuit current is lower than string operating current. Amorphous cell hot spot are tested to develop the techniques required for performing reverse bias testing of amorphous cells. Also, to quantify the response of amorphous cells to reverse biasing. Guidelines are developed from testing for reducing hot spot susceptibility of amorphous modules and to develop a qualification test for hot spot testing of amorphous modules. It is concluded that amorphous cells undergo hot spot heating similarly to crystalline cells. Comparison of results obtained with submodules versus actual modules indicate heating levels lower in actual modules. Module design must address hot spot testing and hot spot qualification test conducted on modules showed no instabilities and minor cell erosion.

  15. Meteorology of Jupiter's Equatorial Hot Spots and Plumes from Cassini

    CERN Document Server

    Choi, David S; Vasavada, Ashwin R; Simon-Miller, Amy A

    2013-01-01

    We present an updated analysis of Jupiter's equatorial meteorology from Cassini observations. For two months preceding the spacecraft's closest approach, the Imaging Science Subsystem (ISS) onboard regularly imaged the atmosphere. We created time-lapse movies from this period in order to analyze the dynamics of equatorial hot spots and their interactions with adjacent latitudes. Hot spots are quasi-stable, rectangular dark areas on visible-wavelength images, with defined eastern edges that sharply contrast with surrounding clouds, but diffuse western edges serving as nebulous boundaries with adjacent equatorial plumes. Hot spots exhibit significant variations in size and shape over timescales of days and weeks. Some of these changes correspond with passing vortex systems from adjacent latitudes interacting with hot spots. Strong anticyclonic gyres present to the south and southeast of the dark areas appear to circulate into hot spots. Impressive, bright white plumes occupy spaces in between hot spots. Compact...

  16. Meteorology of Jupiter's Equatorial Hot Spots and Plumes from Cassini

    Science.gov (United States)

    Choi, David Sanghun; Showman, Adam P.; Vasavada, Ashwin R.; Simon-Miller, Amy A.

    2013-01-01

    We present an updated analysis of Jupiter's equatorial meteorology from Cassini observations. For two months preceding the spacecraft's closest approach, the Imaging Science Subsystem (ISS) onboard regularly imaged the atmosphere. We created time-lapse movies from this period in order to analyze the dynamics of equatorial hot spots and their interactions with adjacent latitudes. Hot spots are relatively cloud-free regions that emit strongly at 5 lm; improved knowledge of these features is crucial for fully understanding Galileo probe measurements taken during its descent through one. Hot spots are quasistable, rectangular dark areas on visible-wavelength images, with defined eastern edges that sharply contrast with surrounding clouds, but diffuse western edges serving as nebulous boundaries with adjacent equatorial plumes. Hot spots exhibit significant variations in size and shape over timescales of days and weeks. Some of these changes correspond with passing vortex systems from adjacent latitudes interacting with hot spots. Strong anticyclonic gyres present to the south and southeast of the dark areas appear to circulate into hot spots. Impressive, bright white plumes occupy spaces in between hot spots. Compact cirrus-like 'scooter' clouds flow rapidly through the plumes before disappearing within the dark areas. These clouds travel at 150-200 m/s, much faster than the 100 m/s hot spot and plume drift speed. This raises the possibility that the scooter clouds may be more illustrative of the actual jet stream speed at these latitudes. Most previously published zonal wind profiles represent the drift speed of the hot spots at their latitude from pattern matching of the entire longitudinal image strip. If a downward branch of an equatorially-trapped Rossby wave controls the overall appearance of hot spots, however, the westward phase velocity of the wave leads to underestimates of the true jet stream speed.

  17. An approach for addressing hard-to-detect hot spots.

    Science.gov (United States)

    Abelquist, Eric W; King, David A; Miller, Laurence F; Viars, James A

    2013-05-01

    The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) survey approach is comprised of systematic random sampling coupled with radiation scanning to assess acceptability of potential hot spots. Hot spot identification for some radionuclides may not be possible due to the very weak gamma or x-ray radiation they emit-these hard-to-detect nuclides are unlikely to be identified by field scans. Similarly, scanning technology is not yet available for chemical contamination. For both hard-to-detect nuclides and chemical contamination, hot spots are only identified via volumetric sampling. The remedial investigation and cleanup of sites under the Comprehensive Environmental Response, Compensation, and Liability Act typically includes the collection of samples over relatively large exposure units, and concentration limits are applied assuming the contamination is more or less uniformly distributed. However, data collected from contaminated sites demonstrate contamination is often highly localized. These highly localized areas, or hot spots, will only be identified if sample densities are high or if the environmental characterization program happens to sample directly from the hot spot footprint. This paper describes a Bayesian approach for addressing hard-to-detect nuclides and chemical hot spots. The approach begins using available data (e.g., as collected using the standard approach) to predict the probability that an unacceptable hot spot is present somewhere in the exposure unit. This Bayesian approach may even be coupled with the graded sampling approach to optimize hot spot characterization. Once the investigator concludes that the presence of hot spots is likely, then the surveyor should use the data quality objectives process to generate an appropriate sample campaign that optimizes the identification of risk-relevant hot spots. PMID:23528274

  18. ''Hot spots'': Subnanometer femtosecond energy localization

    International Nuclear Information System (INIS)

    In a condensed energetic material an understanding of the dynamics and microscopic mechanisms underlying energy transfer between a shock front and various defects is of prime importance for a realistic description of ''hot spot'' formation and explosives initiation. A wide variety of simulations using the well-established technique of computer molecular dynamics has enabled us to obtain a general and very useful microscopic description of the processes beneath the macroscopic behavior of shocked systems. The calculation of the influence of heterogeneities such as point and line defects, voids, and grain boundaries is made possible by computer codes that can handle totally heterogeneous dynamical systems and track the dynamics of energy concentration and partitioning among the molecular bonds in the defect and the nearby region. One and two-dimensional calculations will be discussed in which the spatial and temporal dependence of the energy flux in a general lattice-defect system is calculated quantitatively as a function of shock strength, initial temperature, and initial parameters defining the lattice and defect

  19. On the burn topology of hot-spot-initiated reactions

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Larry G [Los Alamos National Laboratory; Zimmermann, Bjorn [WOLFRAM RESEARCH INC.; Nichols, Albert L [LLNL

    2009-01-01

    We determine the reaction progress function for an ideal hot spot model problem. The considered problem has an exact analytic solution that can derived from a reduction of Nichols statistical hot spot model. We perform numerical calculations to verify the analytic solution and to illustrate the error realized in real, finite systems. We show how the baseline problem, which does not distinguish between the reactant and product densities, can be scaled to handle general cases for which the two densities differ.

  20. Modelling propagation of deflagration waves out of hot spots

    Science.gov (United States)

    Partom, Yehuda

    2015-06-01

    It is widely accepted that shock initiation and detonation of heterogeneous explosives come about by a two-step process known as ignition and growth. In the first step a shock sweeping an explosive cell (control volume) creates hot spots that become ignition sites. In the second step deflagration waves (or burn waves) propagate out of those hot spots and transform the reactant in the cell into reaction products. The macroscopic (or average) reaction rate of the reactant in a cell depends on the speed of those deflagration waves and on the average distance between neighbouring hot spots. Here we simulate the propagation of deflagration waves out of hot spots on the mesoscale in axial symmetry using a 2D hydrocode, to which we add heat conduction and bulk reaction. The propagation speed of the deflagration wave depends on both pressure and temperature, where pressure dependence is dominant at low shock level, and temperature dependence is dominant at a higher shock level. From the simulation we obtain deflagration (or burn) fronts emanating out of the hot spots. For intermediate shock levels the deflagration waves consume the explosive between hot spots. For higher shock levels the deflagration waves strengthen to become detonation waves on the mesoscale. From the simulation results we extract average deflagration wave speeds and show how they depend on reaction rate and on other material parameters.

  1. ``Hot spots'' growth on single nanowire controlled by electric charge

    Science.gov (United States)

    Xi, Shaobo; Liu, Xuehua; He, Ting; Tian, Lei; Wang, Wenhui; Sun, Rui; He, Weina; Zhang, Xuetong; Zhang, Jinping; Ni, Weihai; Zhou, Xiaochun

    2016-06-01

    ``Hot spots'' - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. ``hot spots'' on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag+ to form the ``hot spots'' on the nanowire during the GRR. The appearance probability of ``hot spots'' is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent ``hot spots'' is also controlled by the charge, and obeys a model based on Boltzmann distribution. In addition, the distance distribution here has an advantage in electron transfer and energy saving. Therefore, it's necessary to consider the functions of electric charge during the synthesis or application of nanomaterials.``Hot spots'' - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. ``hot spots'' on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag+ to form the ``hot spots'' on the nanowire during the GRR. The appearance probability of ``hot spots'' is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent ``hot spots'' is also controlled by the charge, and obeys a

  2. Hot Spot Detection System Using Landsat 8/OLI Data

    Science.gov (United States)

    Kato, S.; Nakamura, R.; Oda, A.; Iijima, A.; Kouyama, T.; Iwata, T.

    2015-12-01

    We developed a simple algorithm and a Web-based visualizing system to detect hot spots using Landsat 8 OLI multispectral data as one of the applications of the real-time processing of Landsat 8 data. An empirical equation and radiometric and reflective thresholds were derived to detect hot spots using the OLI data at band 5 (0.865 μm) and band 7 (2.200 μm) based on the increase in spectral radiance at shortwave infrared (SWIR) region due to the emission from objects with high surface temperature. We surveyed typical patterns of surface spectra using the ASTER spectral library to delineate a threshold to distinguish hot spots from background surfaces. To adjust the empirical coefficients of our detection algorithm, we visually inspected the detected hot spots using 6593 Landsat 8 scenes, which cover eastern part of East Asia, taken from January 1, 2014 to December 31, 2014, displayed on a dedicated Web GIS system. Eventually we determined threshold equations which can theoretically detect hot spots at temperatures above 230 °C over isothermal pixels and hot spots as small as 1 m2 at temperatures of 1000 °C as the lowest temperature and the smallest subpixel coverage, respectively, for daytime scenes. The algorithm detected hot spots including wildfires, volcanos, open burnings and factories. 30-m spatial resolution of Landsat 8 enabled to detect wild fires and open burnings accompanied by clearer shapes of fire front lines than MODIS and VIIRS fire products. Although the 16-day revisit cycle of Landsat 8 is too long to effectively find unexpected wildfire or outbreak of eruption, the revisit cycle is enough to monitor temporally stable heat sources, such as continually erupting volcanos and factories. False detection was found over building rooftops, which have relatively smooth surfaces at longer wavelengths, when specular reflection occurred at the satellite overpass.

  3. Integrating sustainable hunting in biodiversity protection in Central Africa: hot spots, weak spots, and strong spots.

    Science.gov (United States)

    Fa, John E; Olivero, Jesús; Farfán, Miguel Ángel; Márquez, Ana Luz; Vargas, Juan Mario; Real, Raimundo; Nasi, Robert

    2014-01-01

    Wild animals are a primary source of protein (bushmeat) for people living in or near tropical forests. Ideally, the effect of bushmeat harvests should be monitored closely by making regular estimates of offtake rate and size of stock available for exploitation. However, in practice, this is possible in very few situations because it requires both of these aspects to be readily measurable, and even in the best case, entails very considerable time and effort. As alternative, in this study, we use high-resolution, environmental favorability models for terrestrial mammals (N = 165) in Central Africa to map areas of high species richness (hot spots) and hunting susceptibility. Favorability models distinguish localities with environmental conditions that favor the species' existence from those with detrimental characteristics for its presence. We develop an index for assessing Potential Hunting Sustainability (PHS) of each species based on their ecological characteristics (population density, habitat breadth, rarity and vulnerability), weighted according to restrictive and permissive assumptions of how species' characteristics are combined. Species are classified into five main hunting sustainability classes using fuzzy logic. Using the accumulated favorability values of all species, and their PHS values, we finally identify weak spots, defined as high diversity regions of especial hunting vulnerability for wildlife, as well as strong spots, defined as high diversity areas of high hunting sustainability potential. Our study uses relatively simple models that employ easily obtainable data of a species' ecological characteristics to assess the impacts of hunting in tropical regions. It provides information for management by charting the geography of where species are more or less likely to be at risk of extinction from hunting. PMID:25372705

  4. SYSTEMATIC AND DYNAMIC PROPER-TIES OF CASTING HOT SPOT

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The variation of casting hot spot with proceeding of solidification and components of casting-mold system is studied by the technique of numerical simulation of solidification.The result shows that the thickest part of casting is not exactly the last part of solidification in the casting, while the last part of solidification is not exactly casting hot spot at the early stage of solidification.The location, size, shape and number of casting hot spot change with geomitric, physical and technological factors of the casting-mold system such as thickness of the casting secondary wall and with the passage of time in the course of the solidification.The former is known as the systematic property of hot spot and the latter, dynamic property.Only when the properties of hot spot are grasped completely and accurately, can it be fed more effectively.By doing so, not only sound castings can be obtained, but also riser efficiency can be improved.

  5. "Hot spots" growth on single nanowire controlled by electric charge.

    Science.gov (United States)

    Xi, Shaobo; Liu, Xuehua; He, Ting; Tian, Lei; Wang, Wenhui; Sun, Rui; He, Weina; Zhang, Xuetong; Zhang, Jinping; Ni, Weihai; Zhou, Xiaochun

    2016-06-01

    "Hot spots" - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. "hot spots" on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag(+) to form the "hot spots" on the nanowire during the GRR. The appearance probability of "hot spots" is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent "hot spots" is also controlled by the charge, and obeys a model based on Boltzmann distribution. In addition, the distance distribution here has an advantage in electron transfer and energy saving. Therefore, it's necessary to consider the functions of electric charge during the synthesis or application of nanomaterials. PMID:27240743

  6. Cygnus A: A Long Wavelength Resolution of the Hot Spots

    CERN Document Server

    Lazio, T J W; Kassim, N E; Perley, R A; Erickson, W C; Carilli, C L; Crane, P C

    2006-01-01

    This paper presents observations of Cygnus A at 74 and 327 MHz at angular resolutions of approximately 10" and 3", respectively. These observations are among the highest angular resolutions obtained below 1000 MHz for this object. While the angular resolution at 74 MHz is not sufficient to separate clearly the hot spots from the lobes, guided by 151 and 327 MHz images, we have estimated the 74 MHz emission from the hot spots. We confirm that the emission from both the western and eastern hot spots flattens at low frequencies and that there is a spectral asymmetry between the two. For the eastern hot spot, a low-energy cutoff in the electron energy spectrum appears to explain the flattening, which implies a cutoff Lorentz factor \\gamma_min ~ 300, though we cannot exclude the possibility that there might be a moderate level of free-free absorption. For the western hot spot, the current observations are not sufficient to distinguish between a free-free absorped power-law spectrum and a synchrotron self-absorbed ...

  7. Micro-topography creates biogeochemical hot spots in wetlands

    Science.gov (United States)

    Bhattacharya, Atreyee

    2012-10-01

    Interventions in wetlands could improve water quality, as wetlands regulate not only nutrients such as nitrogen and sulfur but also pollutants in the waters that flow through them. Biological and chemical processes maintain conditions for redox reactions in the wetlands that control the concentration of certain solutes, including nutrients and pollutants. But such biogeochemical processes are not evenly distributed and often are localized in “hot spots” or take place in bouts known as “hot moments.” How these hot spots or hot moments arise remains poorly understood and is often explained by simply evoking variations in soil properties in the wetlands.

  8. Models and methods for hot spot safety work

    DEFF Research Database (Denmark)

    Vistisen, Dorte

    2002-01-01

    Despite the fact that millions DKK each year are spent on improving roadsafety in Denmark, funds for traffic safety are limited. It is therefore vital to spend the resources as effectively as possible. This thesis is concerned with the area of traffic safety denoted "hot spot safety work", which...... is the task of improving road safety through alterations of the geometrical and environmental characteristics of the existing road network. The presently applied models and methods in hot spot safety work on the Danish road network were developed about two decades ago, when data was more limited and software...... and statistical methods less developed. The purpose of this thesis is to contribute to improving "State of the art" in Denmark. Basis for the systematic hot spot safety work are the models describing the variation in accident counts on the road network. In the thesis hierarchical models disaggregated on time...

  9. Analysis of structural hot-spot stress in orthotropic plates

    Institute of Scientific and Technical Information of China (English)

    Chen Ce; Ji Bohai; Xu Hanjiang

    2012-01-01

    On the basis of the actual steel deck structure of Taizhou Bridge, this paper carries out hot-spot stress analysis on some key spots by using the finite element model which simulates local structure of orthotropic steel bridge decks. A finite element model is established for local structure of orthotropic steel bridge decks, and in the analysis of linear elasticity of the structure, face load is employed to simulate the loads from vehicle wheels. Analysis results show that main stresses are relatively heavy at the joints between diaphragm plates, top plates and U-shaped ribs and the joints between diaphragm plates and U-shaped ribs. These joints shall be regarded as key points for hot-spot stress analysis. Different mesh densities are adopted in the finite element model and the main stresses at different hot spots are contrasted and linear extrapolation is carried out using extrapolation formulae. Results show that different mesh densities have different influences on the hot-spot stresses at the welded seams of U-shaped ribs. These influences shall be considered in calculation and analysis.

  10. Plasmonic electromagnetic hot spots temporally addressed by photoinduced molecular displacement.

    Energy Technology Data Exchange (ETDEWEB)

    Juan, M. L.; Plain, J.; Bachelot, R.; Vial, A.; Royer, P.; Gray, S. K.; Montgomery, J. M.; Wiederrecht, G. P.; Univ. de Technologie de Troyes

    2009-04-23

    We report the observation of temporally varying electromagnetic hot spots in plasmonic nanostructures. Changes in the field amplitude, position, and spatial features are induced by embedding plasmonic silver nanorods in the photoresponsive azo-polymer. This polymer undergoes cis?trans isomerization and wormlike transport within resonant optical fields, producing a time-varying local dielectric environment that alters the locations where electromagnetic hot spots are produced. Finite-difference time-domain and Monte Carlo simulations that model the induced field and corresponding material response are presented to aid in the interpretation of the experimental results. Evidence for propagating plasmons induced at the ends of the rods is also presented.

  11. Variability of Jupiter's Five-Micron Hot Spot Inventory

    Science.gov (United States)

    Yanamandra-Fisher, Padma A.; Orton, G. S.; Wakefield, L.; Rogers, J. H.; Simon-Miller, A. A.; Boydstun, K.

    2012-01-01

    Global upheavals on Jupiter involve changes in the albedo of entire axisymmetric regions, lasting several years, with the last two occurring in 1989 and 2006. Against this backdrop of planetary-scale changes, discrete features such as the Great Red Spot (GRS), and other vortices exhibit changes on shorter spatial- and time-scales. We track the variability of the discrete equatorial 5-micron hot spots, semi-evenly spaced in longitude and confined to a narrow latitude band centered at 6.5degN (southern edge of the North Equatorial Belt, NEB), abundant in Voyager images. Tantalizingly similar patterns were observed in the visible (bright plumes and blue-gray regions), where reflectivity in the red is anti-correlated with 5-microns thermal radiance. Ortiz et al. (1998, GRL, 103) characterized the latitude and drift rates of the hot spots, including the descent of the Galileo probe at the southern edge of a 5-micron hot spot, as the superposition of equatorial Rossby waves, with phase speeds between 99 - 103m/s, relative to System III. We note that the high 5-micron radiances correlate well but not perfectly with high 8.57-micron radiances. Because the latter are modulated primarily by changes in the upper ammonia (NH3) ice cloud opacity, this correlation implies that changes in the ammonia ice cloud field may be responsible for the variability seen in the 5-m maps. During the NEB fade (2011 - early 2012), however, these otherwise ubiquitous features were absent, an atmospheric state not seen in decades. The ongoing NEB revival indicates nascent 5-m hot spots as early as April 2012, with corresponding visible dark spots. Their continuing growth through July 2012 indicates the possit.le re-establishment of Rossby waves. The South Equatorial Belt (SEB) and NEB revivals began similarly with an instability that developed into a major outbreak, and many similarities in the observed propagation of clear regions.

  12. Hot Spots, Difficult Spots and Bright Spots——Comments on the 2004 world situation

    Institute of Scientific and Technical Information of China (English)

    YangHongxi; WangWei

    2004-01-01

    While the year of 2004 has witnessed a stable situation in the world as a whole, the interlocked unilateralism, hegemonism, terrorism and regional hot spots have never ceased making troubles that have continued to startle the world. Around the U.S. presidential election, the U.S. foreign strategy and the development of the Middle East situation, the

  13. Hot spot maps of forest presence in the Mediterranean basin

    Directory of Open Access Journals (Sweden)

    Noce S

    2016-06-01

    Full Text Available The Mediterranean basin is one of the most varied areas worldwide in terms of biodiversity and species richness due to its climatic and geomorphological features, and it is characterized by multi-faceted habitats where forests play a crucial role. Nowadays, the geographic distribution of forest species is well known and multiple geographic datasets are available with different spatial details. However, protection and conservation strategies need more specific information to identify areas with high conservation priority or more vulnerable to the ongoing environmental change (“hot spots”. To this purpose, tree species distribution data were investigated through hot spot analysis using Geographic Information Systems. The analysis was carried out on presence data of ten relevant forest tree species/classes across Mediterranean Europe. By combining spatial analysis and spatial statistics, we identified high and very high hot spot areas for the selected species/classes, which were validated by assessing their biological significance. Given the sub-continental extent of the study, a multiple scale approach was applied ranging from regional, sub-regional to local scale, coherently with the potential multi-level and multi-sector users of similar data and tools. Our results confirm the feasibility of the approach used to increase the quality and quantity of information achievable from available forest distribution datasets. The hot spot maps obtained are a useful support for further spatial evaluations, and may help environmental decision makers to identify priority areas for forest protection and conservation.

  14. Structural hot spots for the solubility of globular proteins.

    Science.gov (United States)

    Ganesan, Ashok; Siekierska, Aleksandra; Beerten, Jacinte; Brams, Marijke; Van Durme, Joost; De Baets, Greet; Van der Kant, Rob; Gallardo, Rodrigo; Ramakers, Meine; Langenberg, Tobias; Wilkinson, Hannah; De Smet, Frederik; Ulens, Chris; Rousseau, Frederic; Schymkowitz, Joost

    2016-01-01

    Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID:26905391

  15. Magnetic hot-spots in hollow silicon cylinders

    Science.gov (United States)

    Baryshnikova, K. V.; Evlyukhin, A. B.; Shalin, A. S.

    2016-08-01

    Silicon nanoparticles can possess magnetic Mie-resonant response in the visible and near infrared wavelength ranges. In this paper, we consider numerically the features of magnetic hot-spots realized inside silicon nanocylinders at the conditions of the optical magnetic resonances, and show that the intensity of the magnetic field inside nanoparticles with a coaxial through hole can be much stronger than the intensity of incident light waves.

  16. Distinguishing black holes and wormholes with orbiting hot spots

    Science.gov (United States)

    Li, Zilong; Bambi, Cosimo

    2014-07-01

    The supermassive black hole candidates at the center of every normal galaxy might be wormholes created in the early Universe and connecting either two different regions of our Universe or two different universes in a multiverse model. Indeed, the origin of these supermassive objects is not well understood; topological nontrivial structures like wormholes are allowed both in general relativity and in alternative theories of gravity, and current observations cannot rule out such a possibility. In a few years, the VLTI instrument GRAVITY will have the capability to image blobs of plasma orbiting near the innermost stable circular orbit of SgrA*, the supermassive black hole candidate in the Milky Way. The secondary image of a hot spot orbiting around a wormhole is substantially different from that of a hot spot around a black hole, because the photon capture sphere of the wormhole is much smaller. The radius of the photon capture sphere is independent of the hot spot model, and therefore its possible detection, which is observationally challenging but not out of reach, can unambiguously test if the center of our Galaxy harbors a wormhole rather than a black hole.

  17. Real-time satellite monitoring of volcanic hot spots

    Science.gov (United States)

    Harris, Andrew J. L.; Flynn, Luke P.; Dean, Ken; Pilger, Eric; Wooster, Martin; Okubo, Chris; Mouginis-Mark, Peter; Garbeil, Harold; Thornber, Carl; De la Cruz-Reyna, Servando; Rothery, Dave; Wright, Robert

    Direct satellite data reception at high temporal frequencies and automated processing enable near-real-time, near-continuous thermal monitoring of volcanoes. We review what has been achieved in terms of turning this capability into real-time tools of use to volcano monitoring agencies. Current capabilities focus on 2 instruments: the advanced very high resolution radiometer (AVHRR) and the Geostationary Operational Environmental Satellite (GOES) imager. Collection of lO AVHRR images per day covering Alaska, the Aleutians, and Kamchatka allows routine, on-reception analysis of volcanic hot spots across this region. Data collected between 1996 and 1998 detected 302 hot spots due to lava flows, lava domes, pyroclastic flows, fumaroles, and geothermally heated lakes at 12 different volcanoes. Information was used for hazard mitigation by the Alaskan Volcano Observatory. GOES provides data for North and South American volcanoes every 15-30 minutes. Automated processing allows eruption information and alerts to be posted on the Internet within 15-60 minutes of reception. We use June 1998 to demonstrate the frequency of data acquisition. During this month 2879 GOES images were collected from which 14,832 sub-images of 6 active volcanoes were processed. Although 82% (12,200) of these sub-images were cloud covered, hot spots were still evident on 11% (1634) of the sub-images. Analysis of GOES data for 1998 identified hot spots due to (1) lava flows at Kilauea and Cerro Azul, (2) dome extrusion and explosive activity at Lascar, Popocatepetl, Colima and Pacaya, and (3) dome cooling and collapse at Soufriere Hills. We were also able to suggest that reports of lava flow activity at Cerro Negro were false. This information was supplied to, and used by, various agencies whose task it is to monitor these volcanoes. Global thermal monitoring will become a reality with the launch of the Earth Observing System's moderate resolution imaging spectrometer (MODIS). An automated thermal

  18. Variation in the Deep Gas Composition in Hot Spots on Jupiter

    Science.gov (United States)

    Bjoraker, Gordon; de Pater, Imke; Wong, Michael H.; Adamkovics, Mate; Hewagama, Tilak; Hesman, Brigette

    2015-11-01

    We used CSHELL on NASA’s Infrared Telescope Facility and NIRSPEC on the Keck telescope in the last two years to spectrally resolve line profiles of CH3D, NH3, PH3, and H2O in 5-micron Hot Spots on Jupiter. The profile of the CH3D lines at 4.66 microns is very broad in both NEB and SEB Hot Spots due to collisions with up to 8 bars of H2, where unit optical depth occurs due to collision-induced H2 opacity. The extreme width of these CH3D features implies that the Hot Spots that we observed do not have significant cloud opacity for P > 2 bars. We retrieved NH3, PH3, and gaseous H2O within Hot Spots in both the NEB and SEB. We had dry nights on Mauna Kea and a sufficient Doppler shift to detect H2O. We will compare line wings to derive H2O profiles in the 2 to 6-bar region. NEB Hot Spots are depleted in NH3 with respect to adjacent regions. Interestingly, SEB Hot Spots exhibit stronger NH3 absorption than NEB Hot Spots. In addition, SEB Hot Spots have very similar 5-micron spectra as neighboring longitudes in the SEB, implying similar deep gas composition. The dynamical origin of SEB Hot Spots is much less studied than that of NEB Hot Spots, so our observations of gas composition in both regions may constrain mechanisms for forming Hot Spots.

  19. Inhibition of turbulence in inertial-confinement-fusion hot spots by viscous dissipation

    Science.gov (United States)

    Weber, C. R.; Clark, D. S.; Cook, A. W.; Busby, L. E.; Robey, H. F.

    2014-05-01

    Achieving ignition in inertial confinement fusion (ICF) requires the formation of a high-temperature (>10 keV) central hot spot. Turbulence has been suggested as a mechanism for degrading the hot-spot conditions by altering transport properties, introducing colder, mixed material, or reducing the conversion of radially directed kinetic energy to hot-spot heating. We show, however, that the hot spot is very viscous, and the assumption of turbulent conditions in the hot spot is incorrect. This work presents the first high-resolution, three-dimensional simulations of National Ignition Facility (NIF) implosion experiments using detailed knowledge of implosion dynamics and instability seeds and including an accurate model of physical viscosity. We find that when viscous effects are neglected, the hot spot can exhibit a turbulent kinetic energy cascade. Viscous effects, however, are significant and strongly damp small-scale velocity structures, with a hot-spot Reynolds number in the range of only 10--100.

  20. Protein hot spots at bio-nano interfaces

    Directory of Open Access Journals (Sweden)

    Gerald F. Audette

    2011-07-01

    Full Text Available Nanotechnology has influenced the direction of research across the sciences, medicine, and engineering. Carbon nanotubes (CNTs and, more recently, protein nanotubes (PNTs and protein-inorganic nanocomposites have received considerable attention due to their unique nanostructures that can be utilized as a scaffold to house proteins or create nanowires. A shift towards protein-inorganic interactions has numerous applications from biosensors to biofuel cells and bio-based nanodevices. We examine several systems where protein hot spots, the active domains on proteins and the interactive dynamics in them, play a critical role in the interactions at the interface of these unique systems.

  1. PEBBED ANALYSIS OF HOT SPOTS IN PEBBLE-BED REACTORS

    Energy Technology Data Exchange (ETDEWEB)

    Abderrafi M. Ougouag; Hans D. Gougar; William K. Terry; Frederik Reitsma; Wessel Joubert

    2005-09-01

    The Idaho National Laboratory’s PEBBED code and simple probability considerations are used to estimate the likelihood and consequences of the accumulation of highly reactive pebbles in the region of peak power in a pebble-bed reactor. The PEBBED code is briefly described, and the logic of the probability calculations is presented in detail. The results of the calculations appear to show that hot-spot formation produces only moderate increases in peak accident temperatures, and no increases at all in normal operating temperatures.

  2. Magnetised Accretion Discs in Kerr Spacetimes II: Hot Spots

    CERN Document Server

    García, Federico; Johannsen, Tim

    2015-01-01

    Context. Quasi-periodic variability has been observed in a number of X-ray binaries harboring black hole candidates. In general relativity, black holes are uniquely described by the Kerr metric and, according to the cosmic censorship conjecture, curvature singularities always have to be clothed by an event horizon. Aims. In this paper, we study the effect of an external magnetic field on the observed light curves of orbiting hot spots in thin accretion discs around Kerr black holes and naked singularities. Methods. We employ a ray-tracing algorithm to calculate the light curves and power spectra of such hot spots as seen by a distant observer for uniform and dipolar magnetic field configurations assuming a weak coupling between the magnetic field and the disc matter. Results. We show that the presence of an external dipolar magnetic field leads to potentially observable modifications of these signals for both Kerr black holes and naked singularities, while an external uniform magnetic field has practically no...

  3. AY Ceti - A flaring, spotted star with a hot companion

    Science.gov (United States)

    Simon, T.; Fekel, F. C., Jr.; Gibson, D. M.

    1985-01-01

    AY Ceti is a late-type single-line spectroscopic binary, a bright X-ray source (L/x/ equal to about 1.5 x 10 to the 31st ergs/s), and a spotted star, as evidenced by its prominent photometric wave. In this paper, observations made with the IUE satellite and the VLA radio interferometer are reported. The 1200-2000 A UV spectrum of AY Cet shows a hot stellar continuum and a very broad Ly-alpha absorption line from a previously unobserved white dwarf secondary. The UV spectrum can be matched to the energy distribution of a (T/eff/ = 18,000 K, log g = 8) model atmosphere. Superposed on this hot continuum are high-excitation emission lines typical of chromospheres and transition regions of active late-type stars, e.g., the spotted RS CVn binaries. It is concluded that the bright lines and soft X-ray emission of AY Cet arise from the cool primary star, rather than from mass transfer and accretion onto the secondary as has recently been proposed for the similar system 56 Peg. Two strong radio flares on AY Cet were observed. The second was rapidly variable and left-hand circularly polarized at levels up to pi(c) = 86 + or - 5 percent at 20 cm wavelength. The most likely emission mechanism is an electron-cyclotron maser.

  4. Microblog Hot Spot Mining Based on PAM Probabilistic Topic Model

    Directory of Open Access Journals (Sweden)

    Zheng Yaxin

    2015-01-01

    Full Text Available Microblogs are short texts carried with limited information, which will increase the difficulty of topic mining. This paper proposes the use of PAM (Pachinko Allocation Model probabilistic topic model to extract the generative model of text’s implicit theme for microblog hot spot mining. First, three categories of microblog and the main contribution of this paper are illustrated. Second, for there are four topic models which are respectively explained, the PAM model is introduced in detail in terms of how to generate a document, the accuracy of document classification and the topic correlation in PAM. Finally, MapReduce is described. For the number of microblogs is huge as well as the number of contactors, the totally number of words is relatively small. With MapReduce, microblogs data are split by contactor, document-topic count matrix and contactor-topic count matrix can be locally stored while the word-topic count matrix must be globally stored. Thus, the hot spot mining can be achieved on the basis of PAM probabilistic topic model.

  5. Detecting traffic hot spots using vehicle tracking data

    Science.gov (United States)

    Xu, Zhimin; Lin, Zhiyong; Zhou, Cheng; Huang, Changqing

    2016-03-01

    Vehicle tracking data for thousands of urban vehicles and the availability of digital map provide urban planners unprecedented opportunities for better understanding urban transportation. In this paper, we aim to detect traffic hot spots on urban road networks using vehicle tracking data. Our approach first proposes an integrated map-matching algorithm based on the road buffer and vehicle driving direction, to find out which road segment the vehicle is travelling on. Then, we estimate travel speed by calculating the average the speed of every vehicle on a certain road segment, which indicates traffic status, and create the spatial weights matrices based on the connectivity of road segments, which expresses the spatial dependence between each road segment. Finally, the measure of global and local spatial autocorrelation is used to evaluate the spatial distribution of the traffic condition and reveal the traffic hot spots on the road networks. Experiments based on the taxi tracking data and urban road network data from Wuhan have been performed to validate the detection effectiveness.

  6. Distinguishing black holes and wormholes with orbiting hot spots

    CERN Document Server

    Li, Zilong

    2014-01-01

    The supermassive black hole candidates at the center of every normal galaxy might be wormholes created in the early Universe and connecting either two different regions of our Universe or two different universes in a Multiverse model. Indeed, the origin of these supermassive objects is not well understood, topological non-trivial structures like wormholes are allowed both in general relativity and in alternative theories of gravity, and current observations cannot rule out such a possibility. In a few years, the VLTI instrument GRAVITY will have the capability to image blobs of plasma orbiting near the innermost stable circular orbit of SgrA$^*$, the supermassive black hole candidate in the Milky Way. The secondary image of a hot spot orbiting around a wormhole is substantially different from the one of a hot spot around a black hole, because the photon capture sphere of the wormhole is much smaller, and its detection could thus test if the center of our Galaxy harbors a wormhole rather then a black hole.

  7. Cold spots in neonatal incubators are hot spots for microbial contamination.

    Science.gov (United States)

    de Goffau, Marcus C; Bergman, Klasien A; de Vries, Hendrik J; Meessen, Nico E L; Degener, John E; van Dijl, Jan Maarten; Harmsen, Hermie J M

    2011-12-01

    Thermal stability is essential for the survival and well-being of preterm neonates. This is achieved in neonatal incubators by raising the ambient temperature and humidity to sufficiently high levels. However, potentially pathogenic microorganisms also can thrive in such warm and humid environments. We therefore investigated whether the level of microbial contamination (i.e., the bacterial load) inside neonatal incubators can be predicted on the basis of their average temperature and relative humidity settings, paying special attention to local temperature differences. Swab samples were taken from the warmest and coldest spots found within Caleo incubators, and these were plated to determine the number of microbial CFU per location. In incubators with high average temperature (≥ 34°C) and relative humidity (≥ 60%) values, the level of microbial contamination was significantly higher at cold spots than at hot spots. This relates to the fact that the local equilibrium relative humidity at cold spots is sufficiently high to sustain microbial growth. The abundance of staphylococci, which are the main causative agents of late-onset sepsis in preterm neonates, was found to be elevated significantly in cold areas. These findings can be used to improve basic incubator hygiene.

  8. Modeling Hot-Spot Contributions in Shocked High Explosives at the Mesoscale

    Energy Technology Data Exchange (ETDEWEB)

    Harrier, Danielle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-12

    When looking at performance of high explosives, the defects within the explosive become very important. Plastic bonded explosives, or PBXs, contain voids of air and bonder between the particles of explosive material that aid in the ignition of the explosive. These voids collapse in high pressure shock conditions, which leads to the formation of hot spots. Hot spots are localized high temperature and high pressure regions that cause significant changes in the way the explosive material detonates. Previously hot spots have been overlooked with modeling, but now scientists are realizing their importance and new modeling systems that can accurately model hot spots are underway.

  9. Application of hot spot conception to analysis of spectra from reactions with light bombarding nuclei

    International Nuclear Information System (INIS)

    Data collection on the ''hot spot'' formation in nucleus-nuclear collisions and light particle emission from it is obtained. Some indications of the ''hot spot'' existence are received in the course of experimental data analysis - yield cross section of pre-equilibrium neutron escaping forward and spectra of light particles at backward angles. Calculations through the ''hot spot'' mechanism are compared with spectra. The forecast in respect to correlation experiment which may be considered as a critical one for the ''hot spot'' conception is drawn

  10. Vascular design for reducing hot spots and stresses

    Science.gov (United States)

    Rocha, L. A. O.; Lorente, S.; Bejan, A.

    2014-05-01

    This paper is a proposal to embed tree-shaped vasculatures in a wall designed such that the wall withstands without excessive hot spots and peak stresses the intense heating and pressure that impinge on it. The vasculature is a quilt of square-shaped panels, each panel having a tree vasculature that connects the center with the perimeter. The vascular designs for volumetric cooling can be complemented by the shaping and distributing of channels for maximum strength and thermal performance at the same time. Numerical simulations of heat flow and thermal stresses in three directions show that it is possible to determine the optimal geometric features of configurations with radial channels and trees with radial and one level of bifurcations. The global performance is evaluated in terms of the overall thermal resistance and peak von Mises stresses. The dendritic design is superior under the studied thermal condition.

  11. Hot spin spots in the laser-induced demagnetization

    Directory of Open Access Journals (Sweden)

    M. S. Si

    2012-03-01

    Full Text Available Laser-induced femtosecond magnetism or femtomagnetism simultaneously relies on two distinctive contributions: (a the optical dipole interaction (ODI between a laser field and a magnetic system and (b the spin expectation value change (SEC between two transition states. Surprisingly, up to now, no study has taken both contributions into account simultaneously. Here we do so by introducing a new concept of the optical spin generator, a product of SEC and ODI between transition states. In ferromagnetic nickel, our first-principles calculation demonstrates that the larger the value of optical spin generator is, the larger the dynamic spin moment change is. This simple generator directly links the time-dependent spin moment change ΔMzk(t at every crystal-momentum k point to its intrinsic electronic structure and magnetic properties. Those hot spin spots are a direct manifestation of the optical spin generator, and should be the focus of future research.

  12. Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences

    KAUST Repository

    Chen, Peng

    2013-07-23

    Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013 Wiley Periodicals, Inc.

  13. Dynamic programming-based hot spot identification approach for pedestrian crashes.

    Science.gov (United States)

    Medury, Aditya; Grembek, Offer

    2016-08-01

    Network screening techniques are widely used by state agencies to identify locations with high collision concentration, also referred to as hot spots. However, most of the research in this regard has focused on identifying highway segments that are of concern to automobile collisions. In comparison, pedestrian hot spot detection has typically focused on analyzing pedestrian crashes in specific locations, such as at/near intersections, mid-blocks, and/or other crossings, as opposed to long stretches of roadway. In this context, the efficiency of the some of the widely used network screening methods has not been tested. Hence, in order to address this issue, a dynamic programming-based hot spot identification approach is proposed which provides efficient hot spot definitions for pedestrian crashes. The proposed approach is compared with the sliding window method and an intersection buffer-based approach. The results reveal that the dynamic programming method generates more hot spots with a higher number of crashes, while providing small hot spot segment lengths. In comparison, the sliding window method is shown to suffer from shortcomings due to a first-come-first-serve approach vis-à-vis hot spot identification and a fixed hot spot window length assumption. PMID:27209154

  14. Dynamic programming-based hot spot identification approach for pedestrian crashes.

    Science.gov (United States)

    Medury, Aditya; Grembek, Offer

    2016-08-01

    Network screening techniques are widely used by state agencies to identify locations with high collision concentration, also referred to as hot spots. However, most of the research in this regard has focused on identifying highway segments that are of concern to automobile collisions. In comparison, pedestrian hot spot detection has typically focused on analyzing pedestrian crashes in specific locations, such as at/near intersections, mid-blocks, and/or other crossings, as opposed to long stretches of roadway. In this context, the efficiency of the some of the widely used network screening methods has not been tested. Hence, in order to address this issue, a dynamic programming-based hot spot identification approach is proposed which provides efficient hot spot definitions for pedestrian crashes. The proposed approach is compared with the sliding window method and an intersection buffer-based approach. The results reveal that the dynamic programming method generates more hot spots with a higher number of crashes, while providing small hot spot segment lengths. In comparison, the sliding window method is shown to suffer from shortcomings due to a first-come-first-serve approach vis-à-vis hot spot identification and a fixed hot spot window length assumption.

  15. Evidence for the Daxiawan as a hot spot in the Earth

    Institute of Scientific and Technical Information of China (English)

    汤懋苍; 钟大赉; 李文华; 冯松

    1999-01-01

    From the point of view of application, the definition of hot spot was given first. The solid geophysical evidence suggested that the Daxiawan (great gorge) in Yarlung Zangbo River should be a hot spot, which is a special region with high ground temperature, low density, low magnetism, negative gravity abnormality, frequent earthquake and strong tectonics. According to the data available, the center of the hot spot was preliminarily decided. The difference between the ground surface and air temperature in January is negatively correlated with the distance from the hot spot center to the meteorological station. According to the ground surface energy balance equation, the geothermal flux in the center of hot spot is about 25 W/m~2. Further analysis suggested that Daxiawan is a pilot region of climate change as well as the region of the heaviest rainfall and highest latitude of tropical forest in the world.

  16. Experimental Study of Ignition by Hot Spot in Internal Combustion Engines

    Science.gov (United States)

    Serruys, Max

    1938-01-01

    In order to carry out the contemplated study, it was first necessary to provide hot spots in the combustion chamber, which could be measured and whose temperature could be changed. It seemed difficult to realize both conditions working solely on the temperature of the cooling water in a way so as to produce hot spots on the cylinder wall capable of provoking autoignition. Moreover, in the majority of practical cases, autoignition is produced by the spark plug, one of the least cooled parts in the engine. The first procedure therefore did not resemble that which most generally occurs in actual engine operation. All of these considerations caused us to reproduce similar hot spots at the spark plugs. The hot spots produced were of two kinds and designated with the name of thermo-electric spark plug and of metallic hot spot.

  17. Association of poly-purine/poly-pyrimidine sequences with meiotic recombination hot spots

    Directory of Open Access Journals (Sweden)

    Pitt Joel PW

    2006-07-01

    Full Text Available Abstract Background Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py tracts (PPTs, a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported. Results We used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C. Conclusion Our results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic

  18. Hot-Cold Spots in Italian Macroseismic Data

    CERN Document Server

    Molchan, G; Panza, G F

    2010-01-01

    The site effect is usually associated with local geological conditions, which increase or decrease the level of shaking compared with standard attenuation relations. We made an attempt to see in the macroseismic data of Italy some other effects, namely, hot/cold spots in the terminology of Olsen (2000), which are related to local fault geometry rather than to soil conditions. We give a list of towns and villages liable to amplify (+) or to reduce (-) the level of shaking in comparison with the nearby settlements. Relief and soil conditions cannot always account for the anomalous sites. Further, there are sites where both (+) and (-) effects are observed depending on the earthquake. The opposite effects can be generated by events from the same seismotectonic zone and along the same direction to the site. Anomalous sites may group themselves into clusters of different scales. All isolated anomalous patterns presented in this paper can be used in hazard analysis, in particular, for the modeling and testing of se...

  19. HOT SPOT RELIEF WITH EMBEDDED BEAM FOR CDMA SYSTEMS IN HAPS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper proposes a novel micro/macro beam coverage scheme used in High Altitude Platform System (HAPS) Code Division Multiple Access (CDMA) systems. A relief of traffic burden in hot spot areas is achieved by embedding micro-beams into the macro-beams at the hot spot locations, together with appropriate power ratio control and user ratio control. The simulation results show that the hot spot problem can be relieved efficiently with the presented configuration, and a higher and more stable system capacity is expectable despite the variation of user distribution.

  20. Ring of nine Gamma Ray Burst overlap with the hot spot of my hypothesis

    Science.gov (United States)

    Cao, Dayong

    2016-03-01

    During 2004 to 2014, a symmetry axis and a cold spot (a structure of one billion light years across) of CMB were observed, and I supposed there is a hot spot, and there is a symmetry between the cold spot and the hot spot of CMB. http://www.dailymail.co.uk/sciencetech/article-2430415 http://meetings.aps.org/link/BAPS.2014.MAR.Y33.9 In 2015, a Ring of Nine Gamma Ray Burst (a structure of FIVE BILLION light years across) which is a part of structure of double helix and overlap with the hot spot was observed. http://www.dailymail.co.uk/sciencetech/article-3185193 The Ring of Nine Gamma Ray Burst could be explained by the hot spot. There is a balance systemic model with structure of double helix of the flat universe between cold spot and hot spot-a balance between stellar matter and dark massenergy (include dark matter and dark energy). The model can explain of the Hubble's redshift. There is a larger dark hole instead of the huge black hole of the center of the Milky Way galaxy, and a dark hole builds up a balance system with sun. This model should explain of the seasonal Extinctions. http://meetings.aps.org/link/BAPS.2015.APR.H14.8

  1. Magnetised accretion discs in Kerr spacetimes. II. Hot spots

    Science.gov (United States)

    García, Federico; Ranea-Sandoval, Ignacio F.; Johannsen, Tim

    2016-03-01

    Context. Quasi-periodic variability has been observed in a number of X-ray binaries that harbor black hole candidates. In general relativity, black holes are uniquely described by the Kerr metric and, according to the cosmic censorship conjecture, curvature singularities always have to be clothed by an event horizon. Aims: In this paper, we study the observed light curves that arise from orbiting hotspots in thin accretion discs around Kerr black holes and naked singularities, and the effect introduced by the presence of an external magnetic field. Methods: We employ a ray-tracing algorithm to calculate the light curves and power spectra of these hot spots as seen by a distant observer for uniform and dipolar magnetic field configurations, assuming a weak coupling between the magnetic field and the disc matter. Results: We show that the presence of an external dipolar magnetic field leads to potentially observable modifications of these light curves for both Kerr black holes and naked singularities, while an external uniform magnetic field has practically no effect. In particular, we demonstrate that the emission from a hotspot, which is orbiting near the innermost stable circular orbit of a naked singularity in a dipolar magnetic field, can be significantly harder than the emission of the same hotspot in the absence of this type of magnetic field. Conclusions: The comparison of our model with observational data may allow us to study the geometry of magnetic fields around compact objects and to test the cosmic censorship conjecture in conjunction with other observables, such as thermal continuum spectra and iron line profiles.

  2. Controlling surface-plasmon-polaritons launching with hot spot cylindrical waves in a metallic slit structure

    Science.gov (United States)

    Yao, Wenjie; Sun, Chengwei; Gong, Qihuang; Chen, Jianjun

    2016-09-01

    Plasmonic nanostructures, which are used to generate surface plasmon polaritons (SPPs), always involve sharp corners where the charges can accumulate. This can result in strong localized electromagnetic fields at the metallic corners, forming the hot spots. The influence of the hot spots on the propagating SPPs are investigated theoretically and experimentally in a metallic slit structure. It is found that the electromagnetic fields radiated from the hot spots, termed as the hot spot cylindrical wave (HSCW), can greatly manipulate the SPP launching in the slit structure. The physical mechanism behind the manipulation of the SPP launching with the HSCW is explicated by a semi-analytic model. By using the HSCW, unidirectional SPP launching is experimentally realized in an ultra-small metallic step-slit structure. The HSCW bridges the localized surface plasmons and the propagating surface plasmons in an integrated platform and thus may pave a new route to the design of plasmonic devices and circuits.

  3. Hot spot formation and stagnation properties in simulations of direct-drive NIF implosions

    Science.gov (United States)

    Schmitt, Andrew J.; Obenschain, Stephen P.

    2016-05-01

    We investigate different proposed methods of increasing the hot spot energy and radius in inertial confinement fusion implosions. In particular, shock mistiming (preferentially heating the inner edge of the target's fuel) and increasing the initial vapor gas density are investigated as possible control mechanisms. We find that only the latter is effective in substantially increasing the hot spot energy and dimensions while achieving ignition. In all cases an increase in the hot spot energy is accompanied by a decrease in the hot spot energy density (pressure) and both the yield and the gain of the target drop substantially. 2D simulations of increased vapor density targets predict an increase in the robustness of the target with respect to surface perturbations but are accompanied by significant yield degradation.

  4. Calculation of the fast ion tail distribution for a spherically symmetric hot spot

    Science.gov (United States)

    McDevitt, C. J.; Tang, X.-Z.; Guo, Z.; Berk, H. L.

    2014-10-01

    The fast ion tail for a spherically symmetric hot spot is computed via the solution of a simplified Fokker-Planck collision operator. Emphasis is placed on describing the energy scaling of the fast ion distribution function in the hot spot as well as the surrounding cold plasma throughout a broad range of collisionalities and temperatures. It is found that while the fast ion tail inside the hot spot is significantly depleted, leading to a reduction of the fusion yield in this region, a surplus of fast ions is observed in the neighboring cold plasma region. The presence of this surplus of fast ions in the neighboring cold region is shown to result in a partial recovery of the fusion yield lost in the hot spot.

  5. Ion distribution in the hot spot of an inertial confinement fusion plasma

    Science.gov (United States)

    Tang, Xianzhu; Guo, Zehua; Berk, Herb

    2012-10-01

    Maximizing the fusion gain of inertial confinement fusion (ICF) for inertial fusion energy (IFE) applications leads to the standard scenario of central hot spot ignition followed by propagating burn wave through the cold/dense assembled fuel. The fact that the hot spot is surrounded by cold but dense fuel layer introduces subtle plasma physics which requires a kinetic description. Here we perform Fokker-Planck calculations and kinetic PIC simulations for an ICF plasma initially in pressure balance but having large temperature gradient over a narrow transition layer. The loss of the fast ion tail from the hot spot, which is important for fusion reactivity, is quantified by Fokker-Planck models. The role of electron energy transport and the ambipolar electric field is investigated via kinetic simulations and the fluid moment models. The net effect on both hot spot ion temperature and the ion tail distribution, and hence the fusion reactivity, is elucidated.

  6. Calculation of the fast ion tail distribution for a spherically symmetric hot spot

    Energy Technology Data Exchange (ETDEWEB)

    McDevitt, C. J.; Tang, X.-Z.; Guo, Z. [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Berk, H. L. [Department of Physics, University of Texas, Austin, Texas 78712 (United States)

    2014-10-15

    The fast ion tail for a spherically symmetric hot spot is computed via the solution of a simplified Fokker-Planck collision operator. Emphasis is placed on describing the energy scaling of the fast ion distribution function in the hot spot as well as the surrounding cold plasma throughout a broad range of collisionalities and temperatures. It is found that while the fast ion tail inside the hot spot is significantly depleted, leading to a reduction of the fusion yield in this region, a surplus of fast ions is observed in the neighboring cold plasma region. The presence of this surplus of fast ions in the neighboring cold region is shown to result in a partial recovery of the fusion yield lost in the hot spot.

  7. Hot Spots and Hot Times: Wildlife Road Mortality in a Regional Conservation Corridor

    Science.gov (United States)

    Garrah, Evelyn; Danby, Ryan K.; Eberhardt, Ewen; Cunnington, Glenn M.; Mitchell, Scott

    2015-10-01

    Strategies to reduce wildlife road mortality have become a significant component of many conservation efforts. However, their success depends on knowledge of the temporal and spatial patterns of mortality. We studied these patterns along the 1000 Islands Parkway in Ontario, Canada, a 37 km road that runs adjacent to the St. Lawrence River and bisects the Algonquin-to-Adirondacks international conservation corridor. Characteristics of all vertebrate road kill were recorded during 209 bicycle surveys conducted from 2008 to 2011. We estimate that over 16,700 vertebrates are killed on the road from April to October each year; most are amphibians, but high numbers of birds, mammals, and reptiles were also found, including six reptiles considered at-risk in Canada. Regression tree analysis was used to assess the importance of seasonality, weather, and traffic on road kill magnitude. All taxa except mammals exhibited distinct temporal peaks corresponding to phases in annual life cycles. Variations in weather and traffic were only important outside these peak times. Getis-Ord analysis was used to identify spatial clusters of mortality. Hot spots were found in all years for all taxa, but locations varied annually. A significant spatial association was found between multiyear hot spots and wetlands. The results underscore the notion that multi-species conservation efforts must account for differences in the seasonality of road mortality among species and that multiple years of data are necessary to identify locations where the greatest conservation good can be achieved. This information can be used to inform mitigation strategies with implications for conservation at regional scales.

  8. Analysis of microstructure-dependent shock dissipation and hot-spot formation in granular metalized explosive

    Science.gov (United States)

    Chakravarthy, Sunada; Gonthier, Keith A.

    2016-07-01

    Variations in the microstructure of granular explosives (i.e., particle packing density, size, shape, and composition) can affect their shock sensitivity by altering thermomechanical fields at the particle-scale during pore collapse within shocks. If the deformation rate is fast, hot-spots can form, ignite, and interact, resulting in burn at the macro-scale. In this study, a two-dimensional finite and discrete element technique is used to simulate and examine shock-induced dissipation and hot-spot formation within low density explosives (68%-84% theoretical maximum density (TMD)) consisting of large ensembles of HMX (C4H8N8O8) and aluminum (Al) particles (size ˜ 60 -360 μm). Emphasis is placed on identifying how the inclusion of Al influences effective shock dissipation and hot-spot fields relative to equivalent ensembles of neat/pure HMX for shocks that are sufficiently strong to eliminate porosity. Spatially distributed hot-spot fields are characterized by their number density and area fraction enabling their dynamics to be described in terms of nucleation, growth, and agglomeration-dominated phases with increasing shock strength. For fixed shock particle speed, predictions indicate that decreasing packing density enhances shock dissipation and hot-spot formation, and that the inclusion of Al increases dissipation relative to neat HMX by pressure enhanced compaction resulting in fewer but larger HMX hot-spots. Ensembles having bimodal particle sizes are shown to significantly affect hot-spot dynamics by altering the spatial distribution of hot-spots behind shocks.

  9. Avoiding Carbon Bed Hot Spots in Thermal Process Off-Gas Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nick Soelberg; Joe Enneking

    2011-05-01

    Mercury has had various uses in nuclear fuel reprocessing and other nuclear processes, and so is often present in radioactive and mixed (radioactive and hazardous) wastes. Test programs performed in recent years have shown that mercury in off-gas streams from processes that treat radioactive wastes can be controlled using fixed beds of activated sulfur-impregnated carbon, to levels low enough to comply with air emission regulations such as the Hazardous Waste Combustor (HWC) Maximum Achievable Control Technology (MACT) standards. Carbon bed hot spots or fires have occurred several times during these tests, and also during a remediation of tanks that contained mixed waste. Hot spots occur when localized areas in a carbon bed become heated to temperatures where oxidation occurs. This heating typically occurs due to heat of absoption of gas species onto the carbon, but it can also be caused through external means such as external heaters used to heat the carbon bed vessel. Hot spots, if not promptly mitigated, can grow into bed fires. Carbon bed hot spots and fires must be avoided in processes that treat radioactive and mixed waste. Hot spots are detected by (a) monitoring in-bed and bed outlet gas temperatures, and (b) more important, monitoring of bed outlet gas CO concentrations. Hot spots are mitigated by (a) designing for appropriate in-bed gas velocity, for avoiding gas flow maldistribution, and for sufficient but not excessive bed depth, (b) appropriate monitoring and control of gas and bed temperatures and compositions, and (c) prompt implementation of corrective actions if bed hot spots are detected. Corrective actions must be implemented quickly if bed hot spots are detected, using a graded approach and sequence starting with corrective actions that are simple, quick, cause the least impact to the process, and are easiest to recover from.

  10. Identification of hot-spot residues in protein-protein interactions by computational docking

    Directory of Open Access Journals (Sweden)

    Fernández-Recio Juan

    2008-10-01

    Full Text Available Abstract Background The study of protein-protein interactions is becoming increasingly important for biotechnological and therapeutic reasons. We can define two major areas therein: the structural prediction of protein-protein binding mode, and the identification of the relevant residues for the interaction (so called 'hot-spots'. These hot-spot residues have high interest since they are considered one of the possible ways of disrupting a protein-protein interaction. Unfortunately, large-scale experimental measurement of residue contribution to the binding energy, based on alanine-scanning experiments, is costly and thus data is fairly limited. Recent computational approaches for hot-spot prediction have been reported, but they usually require the structure of the complex. Results We have applied here normalized interface propensity (NIP values derived from rigid-body docking with electrostatics and desolvation scoring for the prediction of interaction hot-spots. This parameter identifies hot-spot residues on interacting proteins with predictive rates that are comparable to other existing methods (up to 80% positive predictive value, and the advantage of not requiring any prior structural knowledge of the complex. Conclusion The NIP values derived from rigid-body docking can reliably identify a number of hot-spot residues whose contribution to the interaction arises from electrostatics and desolvation effects. Our method can propose residues to guide experiments in complexes of biological or therapeutic interest, even in cases with no available 3D structure of the complex.

  11. Accounting for "hot spots" and "hot moments" in soil carbon models for water-limited ecosystems

    Science.gov (United States)

    O'Donnell, Frances; Caylor, Kelly

    2010-05-01

    Soil organic carbon (SOC) dynamics in water-limited ecosystems are complicated by the stochastic nature of rainfall and patchy structure of vegetation, which can lead to "hot spots" and "hot moments" of high biological activity. Non-linear models that use spatial and temporal averages of forcing variables are unable to account for these phenomena and are likely to produce biased results. In this study we present a model of SOC abundance that accounts for spatial heterogeneity at the plant scale and temporal variability in soil moisture content at the daily scale. We approximated an existing simulation-based model of SOC dynamics as a stochastic differential equation driven by multiplicative noise that can be solved numerically for steady-state sizes of three SOC pools. We coupled this to a model of water balance and SOC input rate at a point for a given cover type, defined by the number of shrub and perennial grass root systems and canopies overlapping the point. Using a probabilistic description of vegetation structure based on a two dimensional Poisson process, we derived analytical expressions for the distribution of cover types across a landscape and produced weighted averages of SOC stocks. An application of the model to a shortgrass steppe ecosystem in Colorado, USA, replicated empirical data on spatial patterns and average abundance of SOC, whereas a version of the model using spatially averaged forcing variables overestimated SOC stocks by 12%. The model also successfully replicated data from paired desert grassland sites in New Mexico, USA, that had and had not been affected by woody plant encroachment, indicating that the model could be a useful tool for understanding and predicting the effect of woody plant encroachment on regional carbon budgets. We performed a theoretical analysis of a simplified version of the model to estimate the bias introduced by using spatial averages of forcing variables to model SOC stocks across a range of climatic conditions

  12. SU-E-T-393: Investigation of Hot Spots in Tomotherapy 3D Conformal Breast Plan

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Q; Siebers, J; Khandelwal, S [University of Virginia, Charlottesville, VA (United States)

    2014-06-01

    Purpose: The purpose of this study is to determine the root-cause of hotspots inherent to Tomotherapy static beam 3D conformal radiotherapy (3DCRT) for breast treatment. ASTRO (ref here) recommends that IMRT be avoided for breast treatments. Despite Tomotherapy's inherent IMRT-like optimization and delivery, our experience at a Tomotherapy-only site has been that Tomotherapy 3DCRT fail to produce a clinically acceptable plan for 79% of our breast patients. Hot-spots have been one of the major obstacles. Methods: Eight lumpectomy patients were planned according to RTOG-1005 specification. Two or four tangential beams were used for 3DCRT breast planning. To spare the contralateral breast and ipsilateral lung, part of the PTV was not covered by the primary beam, yielding adjacent hot-spots. We hypothesize that the planning system creates hotspots adjacent to the cold spots to yield scatter radiation dose compensation in the blocked region. Various phantom and patient setup were used to test the hypothesis. Results: Hot spots outside of PTV in the range of 135% - 174% were observed for patient plan. It is confirmed that the PTV partial block causes the adjacent hot spot. The root cause is the optimizer quadratic objective function over- weighs improving the cold spot. The IMRT flexibility offered by Tomotherapy is counter-productive in static-beam 3DCRT breast treatment. For phantom case, as the Modulation-Factor increases from 1.1 to 5, the hot spot increases from 110% to 300%. Limiting the 3DCRT intensity modulation is shown to produce clinically acceptable plan. Conclusion: Most of the hot spots in Tomotherapy 3DCRT breast plan originate from the planning-system optimizer attempting to cover PTV cold spots rather than from the beam energy. Altering the objective function could improve clinical acceptability of static beam Tomotherapy 3DCRT.

  13. Prediction of hot spots in protein interfaces using a random forest model with hybrid features.

    Science.gov (United States)

    Wang, Lin; Liu, Zhi-Ping; Zhang, Xiang-Sun; Chen, Luonan

    2012-03-01

    Prediction of hot spots in protein interfaces provides crucial information for the research on protein-protein interaction and drug design. Existing machine learning methods generally judge whether a given residue is likely to be a hot spot by extracting features only from the target residue. However, hot spots usually form a small cluster of residues which are tightly packed together at the center of protein interface. With this in mind, we present a novel method to extract hybrid features which incorporate a wide range of information of the target residue and its spatially neighboring residues, i.e. the nearest contact residue in the other face (mirror-contact residue) and the nearest contact residue in the same face (intra-contact residue). We provide a novel random forest (RF) model to effectively integrate these hybrid features for predicting hot spots in protein interfaces. Our method can achieve accuracy (ACC) of 82.4% and Matthew's correlation coefficient (MCC) of 0.482 in Alanine Scanning Energetics Database, and ACC of 77.6% and MCC of 0.429 in Binding Interface Database. In a comparison study, performance of our RF model exceeds other existing methods, such as Robetta, FOLDEF, KFC, KFC2, MINERVA and HotPoint. Of our hybrid features, three physicochemical features of target residues (mass, polarizability and isoelectric point), the relative side-chain accessible surface area and the average depth index of mirror-contact residues are found to be the main discriminative features in hot spots prediction. We also confirm that hot spots tend to form large contact surface areas between two interacting proteins. Source data and code are available at: http://www.aporc.org/doc/wiki/HotSpot. PMID:22258275

  14. Joule heating hot spot at high latitudes in the afternoon sector

    Science.gov (United States)

    Cai, L.; Aikio, A. T.; Milan, S. E.

    2016-07-01

    The afternoon Joule heating hot spot has been studied statistically by using the EISCAT Svalbard Radar (ESR) measurements at 75.4° Corrected Geomagnetic latitude (CGMLAT) and the OMNI solar wind data base. For a small subset of events, the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) field-aligned current distributions have been available. The main results are as follows. Afternoon Joule heating hot spots are associated with high values of ionospheric electric fields and slightly enhanced Pedersen conductances. The Joule heating hot spot values are larger in summer than in winter, which can be explained by the higher Pedersen conductances during summer than winter. The afternoon Joule heating hot spots are located close to the reversals of the large-scale field-aligned current systems. The most common location is close to the Region 1/Region 2 boundary and those events are associated with sunward convecting F region plasma. In a few cases, the hot spots take place close to the Region 1/Region 0 boundary and then the ionospheric plasma is convecting antisunward. The hot spots may occur both during slow (450 km/s) speed solar wind conditions. During slow-speed solar wind events, the dominant interplanetary magnetic field (IMF) direction is southward, which is the general requirement for the low-latitude magnetic merging at the dayside magnetopause. During high-speed solar wind, also northward IMF conditions appear, but those are associated with large values of the IMF |By| component, making again the dayside magnetopause merging possible. Finally, the measured afternoon hot spot Joule heating rates are not a linear function of the solar wind energy coupling function.

  15. Hydrologic indicators of hot spots and hot moments of mercury methylation along river corridors

    Science.gov (United States)

    Singer, Michael; Harrison, Lee; Donovan, Patrick; Blum, Joel; Marvin-DiPasquale, Mark

    2016-04-01

    The biogeochemical cycling of metals and other contaminants river-floodplain corridors is controlled by microbial activity is often affected by dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, flow history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this process within a Northern California river system that has a legacy of industrial-scale 19th century hydraulic gold mining. In the first known application of this methodology, we combine hydraulic modeling, measurements of Hg species in sediment and biota, and first-order calculations to assess the role of river floodplains in producing monomethylmercury (MMHg), which accumulates in local and migratory biota. We identify areas that represent 'hot spots' (frequently inundated areas of floodplains) and 'hot moments' (floodplain areas inundated for consecutive long periods). We show that the probability of MMHg production in each sector of the river system is dependent on the spatial patterns of overbank flow and drainage, which affect its long-term redox history. MMHg bioaccumulation within the aquatic food web may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn, and there appears to be no end to MMHg production under a regime of increasingly common large floods with extended duration. These findings identify river floodplains as periodic, temporary, yet important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the historical hydrologic record. We suggest that inundation is the primary driver of MMHg production in river corridors and that the entire flow history must be analyzed in terms of magnitude and frequency of inundation in order to accurately assess biogeochemical risks, rather than merely highlighting the

  16. MICROSTRUCTURE AND PROPERTIES OF DEEP CROGENIC TREATMENT ELECTRODES FOR SPOT WELDING HOT DIP GALVANIZED STEEL

    Institute of Scientific and Technical Information of China (English)

    Wu Zhisheng; Liu Cuirong; Wang Jiuhai; Shan Ping; Hu Shengsun; Lian Jinrui

    2005-01-01

    The microstructure and elements distribution of the deep cryogenic treatment electrodes and non-cryogenic treatment electrodes for spot welding hot dip galvanized steel are observed by a scanning electrical microscope. The grain sizes, the resistivity and the hardness of the electrodes before and after deep cryogenic treatment are measured by X-ray diffraction, the DC double arms bridge and the Brinell hardness testing unit respectively. The spot welding process performance of hot dip galvanized steel plate is tested and the relationship between microstructure and physical properties of deep cryogenic treatment electrodes is analyzed. The experimental results show that deep cryogenic treatment makes Cr, Zr in deep cryogenic treatment electrodes emanate dispersedly and makes the grain of deep cryogenic treatment electrodes smaller than non-cryogenic treatment ones so that the electrical conductivity and the thermal conductivity of deep cryogenic treatment electrodes are improved very much, which make spot welding process performance of the hot dip galvanized steel be improved.

  17. Jovian longitudinal asymmetry in Io-related and Europa-related auroral hot spots

    Science.gov (United States)

    Dessler, A. J.; Chamberlain, J. W.

    1979-01-01

    Auroral emissions generated by the Jovian moons Io and Europa, originating at the foot of the magnetic flux tubes of the satellites, may be largely limited to longitudes where the planet's ionospheric conductivity is enhanced. The enhanced conductivity is produced by trapped energetic electrons that drift into the Jovian atmosphere in regions where the planet's magnetic field is anomalously weak. The most active auroral hot-spot emissions lie in a sector of the northern hemisphere defined by decametric radio emission. Weaker auroral hot spots are found in the southern hemisphere along a magnetic conjugate trace. The brightness and the longitude of the Jovian hot spots predicted in this paper are in agreement with observations reported by Atreya et al. (1977).

  18. Wavelength modulated SERS hot spot distribution in 1D nanostructures on metal film

    Science.gov (United States)

    Wang, Lili; Zeng, Xiping; Liu, Ting; Zhang, Xuemei; Wei, Hua; Huang, Yingzhou; Liu, Anping; Wang, Shuxia; Wen, Weijia

    2016-10-01

    Surface plasmons confining strong electromagnetic fields near metal surfaces, well-known as hot spots, provide an extremely efficient platform for surface-enhanced Raman scattering (SERS). In this work, SERS spectra of probing molecules in a silver particle-wire 1D nanostructure on a thin gold film are investigated. The Raman features of SERS spectra collected at the particle-wire joints exhibit an obvious wavelength dependence phenomenon. This result is confirmed electromagnetic field simulation, revealing that hot spot distribution is sensitively influenced by the wavelength of incident light at the joints. Further studies indicate this wavelength dependence of hot spot distribution is immune to influence from the geometric shape of the particle or the angle between wire and particle, which improves fabrication tolerance. This technology may have promising applications in surface plasmon related fields, such as ultrasensors, solar energy and selective surface catalysis.

  19. Il Canyon di Caprera: un hot spot di cetacei nel Mar Tirreno centrale? = Is the Caprera Canyon an hot spot of cetaceans within the central Tyrrhenian Sea?

    OpenAIRE

    Bittau, Luca; Manconi, Renata

    2011-01-01

    Presence of cetaceans was monitored using a platform of opportunity (whale watching) off north eastern Sardinia, jrom summer 2010 to winter 2011. The monitoring consisted in seventeen surveys covering a total of 1930 km. Six cetacean species have been observed, totalizing 49 sightings. Striped dolphin was the most abundant species in the continental slope area. The waters in the Caprera Canyon appear as a potential hot spot of cetaceans and will be surveyed by dedicated campaigns. Moreover...

  20. Testing a class of non-Kerr metrics with hot spots orbiting SgrA*

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dan; Li, Zilong; Bambi, Cosimo, E-mail: danliu12@fudan.edu.cn, E-mail: zilongli@fudan.edu.cn, E-mail: bambi@fudan.edu.cn [Center for Field Theory and Particle Physics and Department of Physics, Fudan University, 220 Handan Road, 200433 Shanghai (China)

    2015-01-01

    SgrA*, the supermassive black hole candidate at the Galactic Center, exhibits flares in the X-ray, NIR, and sub-mm bands that may be interpreted within a hot spot model. Light curves and images of hot spots orbiting a black hole are affected by a number of special and general relativistic effects, and they can be potentially used to check whether the object is a Kerr black hole of general relativity. However, in a previous study we have shown that the relativistic features are usually subdominant with respect to the background noise and the model-dependent properties of the hot spot, and eventually it is at most possible to estimate the frequency of the innermost stable circular orbit. In this case, tests of the Kerr metric are only possible in combination with other measurements. In the present work, we consider a class of non-Kerr spacetimes in which the hot spot orbit may be outside the equatorial plane. These metrics are difficult to constrain from the study of accretion disks and indeed current X-ray observations of stellar-mass and supermassive black hole candidates cannot put interesting bounds. Here we show that near future observations of SgrA* may do it. If the hot spot is sufficiently close to the massive object, the image affected by Doppler blueshift is brighter than the other one and this provides a specific observational signature in the hot spot's centroid track. We conclude that accurate astrometric observations of SgrA* with an instrument like GRAVITY should be able to test this class of metrics, except in the more unlikely case of a small viewing angle.

  1. Elucidation of the dynamics for hot-spot initiation at nonuniform interfaces of highly shocked materials

    Science.gov (United States)

    An, Qi; Zybin, Sergey V.; Goddard, William A., III; Jaramillo-Botero, Andres; Blanco, Mario; Luo, Sheng-Nian

    2011-12-01

    The fundamental processes in shock-induced instabilities of materials remain obscure, particularly for detonation of energetic materials. We simulated these processes at the atomic scale on a realistic model of a polymer-bonded explosive (3,695,375 atoms/cell) and observed that a hot spot forms at the nonuniform interface, arising from shear relaxation that results in shear along the interface that leads to a large temperature increase that persists long after the shock front has passed the interface. For energetic materials this temperature increase is coupled to chemical reactions that lead to detonation. We show that decreasing the density of the binder eliminates the hot spot.

  2. Studies of plasmonic hot-spot translation by a metal-dielectric layered superlens

    DEFF Research Database (Denmark)

    Thoreson, Mark D.; Nielsen, Rasmus Bundgaard; West, Paul R.;

    2011-01-01

    We have studied the ability of a lamellar near-field superlens to transfer an enhanced electromagnetic field to the far side of the lens. In this work, we have experimentally and numerically investigated superlensing in the visible range. By using the resonant hot-spot field enhancements from...... at a wavelength of about 680 nm. Specifically, we discuss our recent experimental and simulation results on the translation of hot spots using a silver-silica layered superlens design. We compare the experimental results with our numerical simulations and discuss the perspectives and limitations of our approach....

  3. Semi-Supervised Transductive Hot Spot Predictor Working on Multiple Assumptions

    KAUST Repository

    Wang, Jingyan

    2014-05-23

    Protein-protein interactions are critically dependent on just a few residues (“hot spots”) at the interfaces. Hot spots make a dominant contribution to the binding free energy and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there exists a need for accurate and reliable computational hot spot prediction methods. Compared to the supervised hot spot prediction algorithms, the semi-supervised prediction methods can take into consideration both the labeled and unlabeled residues in the dataset during the prediction procedure. The transductive support vector machine has been utilized for this task and demonstrated a better prediction performance. To the best of our knowledge, however, none of the transductive semi-supervised algorithms takes all the three semisupervised assumptions, i.e., smoothness, cluster and manifold assumptions, together into account during learning. In this paper, we propose a novel semi-supervised method for hot spot residue prediction, by considering all the three semisupervised assumptions using nonlinear models. Our algorithm, IterPropMCS, works in an iterative manner. In each iteration, the algorithm first propagates the labels of the labeled residues to the unlabeled ones, along the shortest path between them on a graph, assuming that they lie on a nonlinear manifold. Then it selects the most confident residues as the labeled ones for the next iteration, according to the cluster and smoothness criteria, which is implemented by a nonlinear density estimator. Experiments on a benchmark dataset, using protein structure-based features, demonstrate that our approach is effective in predicting hot spots and compares favorably to other available methods. The results also show that our method outperforms the state-of-the-art transductive learning methods.

  4. Narrow-bandwidth high-order harmonics driven by long-duration hot spots

    Science.gov (United States)

    Kozlov, Maxim; Kfir, Ofer; Fleischer, Avner; Kaplan, Alex; Carmon, Tal; Schwefel, Harald G. L.; Bartal, Guy; Cohen, Oren

    2012-06-01

    We predict and investigate the emission of high-order harmonics by atoms that cross intense laser hot spots that last for a nanosecond or longer. An atom that moves through a nanometer-scale hot spot at characteristic thermal velocity can emit high-order harmonics in a similar fashion to an atom that is irradiated by a short-duration (picosecond-scale) laser pulse. We analyze the collective emission from a thermal gas and from a jet of atoms. In both cases, the line shape of a high-order harmonic exhibits a narrow spike with spectral width that is determined by the bandwidth of the driving laser. Finally, we discuss a scheme for producing long-duration laser hot spots with intensity in the range of the intensity threshold for high-harmonic generation. In the proposed scheme, the hot spot is produced by a long laser pulse that is consecutively coupled to a high-quality micro-resonator and a metallic nano-antenna. This system may be used for generating ultra-narrow bandwidth extreme-ultraviolet radiation through frequency up-conversion of a low-cost compact pump laser.

  5. Jovian longitudinal asymmetry in Io-related and Europa-related auroral hot spots

    Energy Technology Data Exchange (ETDEWEB)

    Dessler, A.J.; Chamberlain, J.W.

    1979-06-15

    Jupiter's internal magnetic field is markedly non-dipolar. We propose that Io- or Europa-generated auroral emissions (originating at the foot of either Io's or Europa's magnetic flux tube) are largely restricted to longitudes where Jupiter's ionospheric conductivity is enhanced. Trapped, energetic electrons that drift into Jupiter's atmosphere, in regions where the Jovian magnetic field is anomalously weak, produce the increased conductivity. The longitude range of enchanced auroral hot-spot emissions is thus restricted to an active sector that is determined from dekametric radio emission to lie in the northern hemisphere in the Jovian System III (1965) longitude range of 205/sup 0/ +- 30/sup 0/. Relatively weaker auroral hot spots should occur in the southern hemisphere along the mgnetic conjugate trace covering the longitude range of 215/sup 0/ +- 55/sup 0/. At other longitudes, the brightness of the hot spot should decrease by at least one order of magnitude. These results, with respect to both brightness and longitude, are in accord with the observations of Jovian auroral hot spots reported by Atreya et al. We show that the northern hemisphere foot of either Io's or Europa's magnetic flux tube was in the preferred longitude range (the active sector) at the time of each observation.

  6. CFD analysis of hot spot formation through a fixed bed reactor of Fischer-Tropsch synthesis

    Directory of Open Access Journals (Sweden)

    Hamed Aligolzadeh

    2015-12-01

    Full Text Available One of the interesting methods for conversion of synthesis gas to heavy hydrocarbons is Fischer–Tropsch process. The process has some bottlenecks, such as hot spot formation and low degree of conversion. In this work, computational fluid dynamics technique was used to simulate conversion of synthetic gas and product distribution. Also, hot spot formation in the catalytic fixed-bed reactor was investigated in several runs. Simulation results indicated that hot spot formation occurred more likely in the early and middle part of reactor due to high reaction rates. Based on the simulation results, the temperature of hot spots increased with increase in the inlet temperature as well as pressure. Among the many CFD runs conducted, it is found that the optimal temperature and pressure for Fischer–Tropsch synthesis are 565 K and 20 bar, respectively. As it seems that the reactor shall work very well under optimal conditions, the reaction rates and catalyst duration would simultaneously be maximum .

  7. The Hot Spots Conjecture on a Class of Domains in Rnwith n ≥ 3

    Institute of Scientific and Technical Information of China (English)

    Peng-fei YANG

    2011-01-01

    In this paper,we define a class of domains in Rn.Using the synchronous coupling of reflecting Brownian motion,we obtain the monotonicity property of the solution of the heat equation with the Neumann boundary conditions.We then show that the hot spots conjecture holds for this class of domains.

  8. The choice between cooled tubular reactor models: analysis of the hot spot

    NARCIS (Netherlands)

    Westerink, E.J.; Koster, N.; Westerterp, K.R.

    1990-01-01

    The applicability of the one-dimensional pseudo-homogeneous model of the cooled tubular reactor is studied. Using the two-dimensional model as the more accurate one we compared both models by studying the influence of the design and operating variables on the conditions in the hot spot of the reacto

  9. A novel approach to detect hot-spots in large-scale multivariate data

    Directory of Open Access Journals (Sweden)

    Kendrick Keith M

    2007-09-01

    Full Text Available Abstract Background Progressive advances in the measurement of complex multifactorial components of biological processes involving both spatial and temporal domains have made it difficult to identify the variables (genes, proteins, neurons etc. significantly changed activities in response to a stimulus within large data sets using conventional statistical approaches. The set of all changed variables is termed hot-spots. The detection of such hot spots is considered to be an NP hard problem, but by first establishing its theoretical foundation we have been able to develop an algorithm that provides a solution. Results Our results show that a first-order phase transition is observable whose critical point separates the hot-spot set from the remaining variables. Its application is also found to be more successful than existing approaches in identifying statistically significant hot-spots both with simulated data sets and in real large-scale multivariate data sets from gene arrays, electrophysiological recording and functional magnetic resonance imaging experiments. Conclusion In summary, this new statistical algorithm should provide a powerful new analytical tool to extract the maximum information from complex biological multivariate data.

  10. Antifuse nano-hot-spot device on a suspended membrane for gas sensing applications

    NARCIS (Netherlands)

    Iordache, G.; Holleman, J.; Kovalgin, A.Y.; Jenneboer, A.J.S.M.

    2003-01-01

    We have designed and realized a new antifuse hot-spot device to be used in gas sensing applications. The antifuse structure was realized on a suspended membrane to minimize the heat losses. For the sensing of alkanes a procedure for making a porous alumina layer doped with Platinum was developed. Th

  11. Hot Spots and Trends in Developing China's Tourism Industry

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    It is stated in China's Tourism Development from 2002 to 2004: Analysis and Prediction, written by experts organized by Research Center of Tourism of China Academy of Social Science that eight hot spots have arisen and future trends in Chinese tourism development has been embodied in eight aspects since 2002.

  12. QPO emission from moving hot spots on the surface of neutron stars: a model

    CERN Document Server

    Bachetti, Matteo; Kulkarni, Akshay; Burderi, Luciano; di Salvo, Tiziana

    2009-01-01

    We present recent results of 3D magnetohydrodynamic simulations of neutron stars with small misalignment angles, as regards the features in light curves produced by regular movements of the hot spots during accretion onto the star. In particular, we show that the variation of position of the hot spot created by the infalling matter, as observed in 3D simulations, can produce high frequency Quasi Periodic Oscillations with frequencies associated with the inner zone of the disk. Simulations show that the usual assumption of a fixed hot spot near the polar region is valid only for misalignment angles relatively large. Otherwise, two phenomena challenge the assumption: one is the presence of Rayleigh-Taylor instabilities at the disk-magnetospheric boundary (e.g. Kulkarni & Romanova 2008), which produce tongues of accreting matter that can reach the star almost anywhere between the equator and the polar region; the other one is the motion of the hot spot around the magnetic pole during stable accretion (e.g. R...

  13. THE PROBLEM OF HOT-SPOTS IN MICROWAVE EQUIPMENT USED FOR PREPARATORY TECHNIQUES - THEORY AND PRACTICE

    NARCIS (Netherlands)

    KOK, LP; BOON, ME; SMID, HM

    1993-01-01

    Electron microscopists who wants to use a microwave (MW) oven to stimulate preparatory processes are sooner or later confronted with the problem of hot spots. It soon becomes clear to the user of any MW oven that the energy distribution-thus the speed of absorbing energy, and hence warming up-varies

  14. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation

    DEFF Research Database (Denmark)

    Michaelson, Jacob J.; Shi, Yujian; Gujral, Madhusudan;

    2012-01-01

    De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investi...

  15. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  16. Cassini VIMS Spectra of the Thermal Emission from Hot Spots Along Enceladus South Pole Fissures

    Science.gov (United States)

    Goguen, Jay D.; Buratti, Bonnie J.; Cassini VIMS Team

    2016-10-01

    Most of the south pole fissure region has not been directly illuminated by sunlight since the sub-solar point moved into the northern hemisphere in 2009, thereby eliminating the background of reflected sunlight at VIMS wavelengths and making the fissure thermal emission readily measureable. Since then, VIMS has measured spectra of at least 11 hot spots along the fissures. Most of these measurements were acquired in ride-along mode with CIRS as the prime instrument. During at least 2 encounters, VIMS and CIRS acquired simultaneous or near-simultaneous spectra of the same fissure location. VIMS spectra include multiple hot spots along Damascus, Baghdad, Cairo, and a likely hot spot on Alexandria.All of the VIMS spectra examined to date are consistent with this scenario of a self-regulating fissure maximum T~200 K with brighter VIMS emissions corresponding to fissures up to ~20 m wide. Emission from the warm fissure interior walls dominate the VIMS spectra with <15% contributed by conductive heating of the adjacent terrain at VIMS wavelengths.CIRS spectra report slightly cooler T's due to CIRS increased sensitivity to lower T emission at longer wavelengths and averaging over contributions from both the hottest and cooler areas. Combined analysis of the CIRS and VIMS spectra spanning 3 to 500 micron wavelengths promises to reveal the distribution of [T, area] near the fissures that cannot be spatially resolved. This [T, area] distribution holds the key to understanding how heat is transferred to the surface within a few 100 m of the fissures.The VIMS-detected emission is concentrated in localized hot spots along the fissures and does not seem to be distributed continuously along them. CIRS spectra suggest a more continuous distribution of the emission along the fissure length. Jets locations also are distributed along the fissure length and it appears that the VIMS-detected hot spots in general correlate with jet locations, but not all of the jet locations have been

  17. High-temperature hot spots on Io as seen by the Galileo solid state imaging (SSI) experiment

    Science.gov (United States)

    McEwen, A.S.; Simonelli, D.P.; Senske, D.R.; Klaasen, K.P.; Keszthelyi, L.; Johnson, T.V.; Geissler, P.E.; Carr, M.H.; Belton, M.J.S.

    1997-01-01

    High-temperature hot spots on Io have been imaged at ???50 km spatial resolution by Galileo's CCD imaging system (SSI). Images were acquired during eclipses (Io in Jupiter's shadow) via the SSI clear filter (???0.4-1.0 ??m), detecting emissions from both small intense hot spots and diffuse extended glows associated with Io's atmosphere and plumes. A total of 13 hot spots have been detected over ???70% of Io's surface. Each hot spot falls precisely on a low-albedo feature corresponding to a caldera floor and/or lava flow. The hot-spot temperatures must exceed ???700 K for detection by SSI. Observations at wavelengths longer than those available to SSI require that most of these hot spots actually have significantly higher temperatures (???1000 K or higher) and cover small areas. The high-temperature hot spots probably mark the locations of active silicate volcanism, supporting suggestions that the eruption and near-surface movement of silicate magma drives the heat flow and volcanic activity of Io. Copyright 1997 by the American Geophysical Union.

  18. Fusion yield rate recovery by escaping hot-spot fast ions in the neighboring fuel layer

    Science.gov (United States)

    Tang, Xian-Zhu; McDevitt, C. J.; Guo, Zehua; Berk, H. L.

    2014-02-01

    Free-streaming loss by fast ions can deplete the tail population in the hot spot of an inertial confinement fusion (ICF) target. Escaping fast ions in the neighboring fuel layer of a cryogenic target can produce a surplus of fast ions locally. In contrast to the Knudsen layer effect that reduces hot-spot fusion reactivity due to tail ion depletion, the inverse Knudsen layer effect increases fusion reactivity in the neighboring fuel layer. In the case of a burning ICF target in the presence of significant hydrodynamic mix which aggravates the Knudsen layer effect, the yield recovery largely compensates for the yield reduction. For mix-dominated sub-ignition targets, the yield reduction is the dominant process.

  19. ELIPGRID-PC: A PC program for calculating hot spot probabilities

    International Nuclear Information System (INIS)

    ELIPGRID-PC, a new personal computer program has been developed to provide easy access to Singer's 1972 ELIPGRID algorithm for hot-spot detection probabilities. Three features of the program are the ability to determine: (1) the grid size required for specified conditions, (2) the smallest hot spot that can be sampled with a given probability, and (3) the approximate grid size resulting from specified conditions and sampling cost. ELIPGRID-PC also provides probability of hit versus cost data for graphing with spread-sheets or graphics software. The program has been successfully tested using Singer's published ELIPGRID results. An apparent error in the original ELIPGRID code has been uncovered and an appropriate modification incorporated into the new program

  20. Identification of a new genomic hot spot of evolutionary diversification of protein function.

    Directory of Open Access Journals (Sweden)

    Aline Winkelmann

    Full Text Available Establishment of phylogenetic relationships remains a challenging task because it is based on computational analysis of genomic hot spots that display species-specific sequence variations. Here, we identify a species-specific thymine-to-guanine sequence variation in the Glrb gene which gives rise to species-specific splice donor sites in the Glrb genes of mouse and bushbaby. The resulting splice insert in the receptor for the inhibitory neurotransmitter glycine (GlyR conveys synaptic receptor clustering and specific association with a particular synaptic plasticity-related splice variant of the postsynaptic scaffold protein gephyrin. This study identifies a new genomic hot spot which contributes to phylogenetic diversification of protein function and advances our understanding of phylogenetic relationships.

  1. STUDY ON LOCATION OF HOT SPOT AT TUBE WALL FOR FIRED CYLINDRICAL FURNACE COMBUSTION

    Institute of Scientific and Technical Information of China (English)

    Wang Taiyong; Lu Shizhong; Xü Zhixue

    2004-01-01

    Based on the analysis of heat radiation intensity from flame,a new mathematical model of the tube-wall temperature of heated tubes is devel-oped by taking down-fired,upright-tube cylindrical furnace for example.The proposed mathematical model can be employed to indicate both the position and size of the hot spot at fire-facing wall of heated tube of combustion chamber,and is characteristic of sim-plicity and efficiency.If coupled with thermoelectric couple or infrared viewer,the presented location method of com-bustion hot spot can offer engineers very valuable proposal to keep furnace running more safely.The same is true for any other type of tubular furnaces.

  2. Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

    Directory of Open Access Journals (Sweden)

    Joseph D. Bauman

    2016-01-01

    Full Text Available Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT. The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K by single-wavelength anomalous dispersion (SAD from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

  3. Evaluation of hot spot factors for thermal and hydraulic design of HTTR

    International Nuclear Information System (INIS)

    High Temperature Engineering Test Reactor (HTTR) is a graphite-moderated and helium gas-cooled reactor with 30 MW in thermal power and 950degC in reactor outlet coolant temperature. One of the major items in thermal and hydraulic design of the HTTR is to evaluate the maximum fuel temperature with a sufficient margin from a viewpoint of integrity of coated fuel particles. Hot spot factors are considered in the thermal and hydraulic design to evaluate the fuel temperature not only under the normal operation condition but also under any transient condition conservatively. This report summarizes the items of hot spot factors selected in the thermal and hydraulic design and their estimated values, and also presents evaluation results of the thermal and hydraulic characteristics of the HTTR briefly. (author)

  4. Application of hot-spot stress fatigue analysis to attachments on flexible plate

    Energy Technology Data Exchange (ETDEWEB)

    Dexter, R.J.; Fisher, J.W. [Lehigh Univ., Bethlehem, PA (United States). Center for Advanced Tech. for Large Structural Systems; Tarquinio, J.E. [Greiner, Inc., King of Prussia, PA (United States)

    1994-12-31

    Cyclic axial and bending loads were applied to angle sections which were fillet welded normal to the flange of large box sections at various eccentricities relative to the webs. Local bending of the thin flange plate between the web and the angle leg parallel to the web caused cracking at the angle fillet weld toe. The hot-spot stress range, measured with a strain gage placed adjacent to the weld toe, was plotted with the number of cycles to through-thickness cracking. In some experiments, a membrane stress range was also applied in the direction perpendicular to the dominant hot-spot stress range. The data from the various configurations plot in the same scatterband just above the Category C fatigue design curve. If the angle is aligned with 10 mm eccentricity or less, cracking originates at the weld root. A method to predict the fatigue strength for this case of weld root cracking in eccentric joints is presented.

  5. Non-LTE Modelling of the Structure and Spectra of the Hot Accretion Spots on the Surface of Young Stars

    CERN Document Server

    Dodin, A V

    2014-01-01

    The paper describes the modelling of the structure and spectra of the hot accretion spots on the surface of young stars with taking into account departures from LTE for hydrogen and helium. It has been found that the existence of the ram pressure of the in-falling gas at the outer boundary of the hot spot leads to the Stark broadening of the hydrogen line profiles up to FWHM of about 1000 km/s at the considered accretion parameters. It is shown that taking into account departures from LTE for atoms and ions of carbon and oxygen does not lead to noticeable changes in the structure of the hot spot.

  6. Microscopic examination of hot spots giving rise to nonlinearity in superconducting resonators

    OpenAIRE

    Kurter, Cihan; Zhuravel, Alexander P.; Ustinov, Alexey V.; Anlage, Steven M.

    2011-01-01

    We investigate the microscopic origins of nonlinear rf response in superconducting electromagnetic resonators. Strong nonlinearity appearing in the transmission spectra at high input powers manifests itself through the emergence of jumplike features near the resonant frequency that evolve toward lower quality factor with higher insertion loss as the rf input power is increased. We directly relate these characteristics to the dynamics of localized normal regions (hot spots) caused by microscop...

  7. An analytical model of pipelined circuit switching in hypercubes in the presence of hot spot traffic

    OpenAIRE

    Safaei, F.; Khonsari, A.; Fathy, M.; Ould-Khaoua, M.

    2005-01-01

    Several recent studies have revealed that PCS can provide superior performance characteristics over wormhole switching under uniform traffic. Analytical model of PCS for common networks (e.g., hypercube) under uniform traffic pattern have recently been reported in the literature. In this paper we propose an analytical model of PCS in the hypercube network augmented with virtual channel in the presence of hot spot traffic. The model has a good agreement with simulation experiments.

  8. Managing Instantly Dense Hot Spot Regions in Wireless Cellular Communication Networks

    Directory of Open Access Journals (Sweden)

    Vikas Solanki

    2015-07-01

    Full Text Available In a wireless communication cellular network, call activity can be more intensive in some regions than others. These high-traffic regions are called hot spot regions. In typical deployments of wireless cellular networks, traffic hot spots can arise from the non-uniform geographic distribution of the mobile users, and the heavy-tailed nature of their network usage patterns. These hot spots of activity can degrade system performance, by increasing network utilization, wireless interference, call blocking, and even call dropping from failed handoffs for mobile users. In this paper, a hierarchical cellular communication wireless network is characterized by overlapping the service area for managing the new calls users having different mobility speed. The overlapping property of the hierarchical-network provides the advantages that share the traffic load to improve the performance of wireless cellular networks in the highly populated area where both slow speed users and high speed users are available. Picocells are created that are underlaid to two-tier networks for handling the slow or staying speed visitor (outside registered users. The hierarchical-networks with picocells, microcells and macrocells provide the secondary resource, which provide the services to new calls as well as handoff calls with guard channels by overflow the slow speed visitor users in picocells, slow speed local users in macrocell by sharing the frequency in vertical as well as in horizontal directions. The picocell is installed on four wheeler vehicle may be moved at any place as per necessity and may be utilized to create picocell to handle the load of hot spot area. Such kind of picocell is known as Portable-Picocell (P-Picocell/ P2cell. The call loss probability of new calls is developed through numerical analysis. The proposed schemes are compared with the existing schemes of CAC. Results show that new proposed schemes are more efficient and handle more visitor calls by

  9. Highly Shocked Polymer Bonded Explosives at a Nonplanar Interface: Hot-Spot Formation Leading to Detonation

    OpenAIRE

    An, Qi; Goddard, William A.; Zybin, Sergey V.; Jaramillo-Botero, Andres; Zhou, Tingting

    2013-01-01

    We report reactive molecular dynamics simulations using the ReaxFF reactive force field to examine shock-induced hot-spot formation followed by detonation initiation in realistic (2.7 million atoms) models of polymer bonded explosives (PBX) with nonplanar interfaces. We considered here two energetic materials (EMs) pentaerythritol tetranitrate (PETN), a common EM for PBX, and silicon pentaerythritol tetranitrate (Si-PETN), which is so extremely sensitive that it has not been possible to chara...

  10. The Halo, Hot Spots and Jet / Cloud Interaction of PKS 2153--69

    Science.gov (United States)

    Young, A. J.; Wilson, A. S.; Tingay, S. J.; Heinz, S.

    2004-08-01

    We report Chandra X-ray Observatory and 1.4 GHz Australian Long Baseline Array (LBA) observations of the radio galaxy PKS 2153--69 and its environment. The Chandra image reveals a roughly spherical halo of hot gas extending out to 30 kpc around PKS 2153--69 with two depressions in the X-ray surface brightness corresponding to the radio lobes. Interpreting these depressions as radio plasma filled cavities we infer a jet power of 4 × 1042 erg s-1. Both radio lobe hot spots are detected by Chandra, and the southern hot spot is detected at 1.4 GHz in the LBA observation, providing the highest spatial resolution map of a radio lobe hot spot to date. The hot spot spectra are consistent with a simple synchrotron emission model. The nucleus has an X-ray spectrum typical of a Type 1 AGN, and the LBA observation shows a one-sided nuclear jet on 0.1'' scales. Approximately 10'' northeast of the nucleus X-ray emission is associated with an extra-nuclear cloud that is the site of a jet/cloud interaction. The X-ray emission from the cloud can be divided into two regions; an unresolved western component associated with a knot of radio emission (seen in low resolution maps but not detected at 1.4 GHz), and a spatially resolved eastern component aligned with the pc-scale jet and associated with highly ionized optical line emitting clouds. The X-ray spectrum of the eastern component is predominantly thermal. We discuss jet precession and jet deflection models to account for the steadily increasing position angle from the northern hot spot to the western component of the jet/cloud interaction region to the direction of the pc-scale jet. This work was supported by NASA through contract NAS8-01129, Chandra Postdoctoral Fellowship Award PF3-40026 and a grant from the Research and Development Grants Scheme of the Swinburne University of Technology.

  11. Wood ant nests as hot spots of carbon dioxide production and cold spots of methane oxidation in temperate forests

    Science.gov (United States)

    Jilkova, Veronika; Picek, Tomas; Cajthaml, Tomas; Frouz, Jan

    2016-04-01

    Wood ant nests are known as hot spots of carbon dioxide (CO2) production and are also thought to affect methane (CH4) flux. Stable high temperatures are maintained in ant nests even in cold environments. Here we focused on quantification of CO2 and CH4 flux in wood ant nests, contribution of ants and microbes to CO2 production, properties of nest material that affect CO2 production and the role of ants and microbes in the maintenance of nest temperature. The research was conducted in temperate and boreal forests inhabited by wood ants (Formica s. str.). Gas fluxes were measured either by an infrared gas analyser or a static chamber technique. Ants and nest materials were also incubated in a laboratory. Material properties potentially influencing CO2 flux, such as moisture, nutrient content or temperature were determined. According to the results, CH4 oxidation was lower in wood ant nests than in the surrounding forest soil suggesting that some characteristics of ant nests hinder CH4 oxidation or promote CH4 production. These characteristics were mainly available carbon and nitrogen contents. Wood ant nests clearly are hot spots of CO2 production in temperate forests originating mainly from ant and also from microbial metabolism. Most important properties positively affecting CO2 production were found to be moisture, nutrient content and temperature. Nest temperature is maintained by ant and microbial metabolism; nests from colder environments produce more metabolic heat to maintain similar temperature as nests from warmer environments. In conclusion, as the abundance of wood ant nests in some forests can be very high, ant nests may largely increase heterogeneity in greenhouse gas fluxes in forest ecosystems.

  12. Predictions of hot spot residues at protein-protein interfaces using support vector machines.

    Directory of Open Access Journals (Sweden)

    Stefano Lise

    Full Text Available Protein-protein interactions are critically dependent on just a few 'hot spot' residues at the interface. Hot spots make a dominant contribution to the free energy of binding and they can disrupt the interaction if mutated to alanine. Here, we present HSPred, a support vector machine(SVM-based method to predict hot spot residues, given the structure of a complex. HSPred represents an improvement over a previously described approach (Lise et al, BMC Bioinformatics 2009, 10:365. It achieves higher accuracy by treating separately predictions involving either an arginine or a glutamic acid residue. These are the amino acid types on which the original model did not perform well. We have therefore developed two additional SVM classifiers, specifically optimised for these cases. HSPred reaches an overall precision and recall respectively of 61% and 69%, which roughly corresponds to a 10% improvement. An implementation of the described method is available as a web server at http://bioinf.cs.ucl.ac.uk/hspred. It is free to non-commercial users.

  13. Radiation-induced chromosomal hot spots at G 1 and G 2 stages of human lymphocytes in culture

    Directory of Open Access Journals (Sweden)

    Murugesan R

    2003-01-01

    Full Text Available Radiation-induced chromosomal break points in cultured lymphocytes of normal healthy individuals as well as of those with certain genetic disorders are reported to be localized at certain specific loci (hot spots. These reports are based on studies carried out in lymphocytes irradiated at G 1 stage. The present study examines whether the location of hot spots and the frequency seen in cells irradiated at G 1 are similar to those irradiated at G 2 stage of the cell cycle and also tests whether cells of patients exhibit hot spots on irradiation.The results showed that the radiation induced chromosomal break points to be similar in those irradiated are G 1 and G 2 stages of the cell cycle and also that cells of patients exhibited chromosomal hot spots.

  14. Hot-spot application of biocontrol agents to replace pesticides in large scale commercial rose farms in Kenya

    DEFF Research Database (Denmark)

    Gacheri, Catherine; Kigen, Thomas; Sigsgaard, Lene

    2015-01-01

    Rose (Rosa hybrida L.) is the most important ornamental crop in Kenya, with huge investments in pest management. We provide the first full-scale, replicated experiment comparing cost and yield of conventional two-spotted spider mite (Tetranychus urticae Koch) control with hot-spot applications...... blanket-treated with an acaricide to decrease infestations. Roses subjected to the hot-spot treatment had significantly lower T. urticae infestations compared with conventionally treated roses. In addition, significantly fewer high spider mite infestations were recorded in roses with the hot...... of the predatory mite Phytoseiulus persimilis (Acari: Phytoseidae) in large commercial rose greenhouses. Hot-spot treatments replaced acaricides except at high infestations and the two treatments were applied in seven greenhouses each. With the conventional treatment, acaricides were applied when T. urticae...

  15. Characterization of hot spots for natural chloroform formation: Relevance for groundwater quality

    Science.gov (United States)

    Jacobsen, Ole S.; Albers, Christian N.; Laier, Troels

    2015-04-01

    Chloroform soil hot spot may deteriorate groundwater quality and may even result in chloroform concentration exceeding the Danish maximum limit of 1 µg/L in groundwater for potable use. In order to characterize the soil properties important for the chloroform production, various ecosystems were examined with respect to soil air chloroform and soil organic matter type and content. Coniferous forest areas, responsible for highest chloroform concentrations, were examined on widely different scales from km to cm scale. Furthermore, regular soil gas measurements including chloroform were performed during 4 seasons at various depths, together with various meteorological measurements and soil temperature recordings. Laboratory incubation experiments were also performed on undisturbed soil samples in order to examine the role of various microbiota, fungi and bacteria. To identify hot spots responsible for the natural contamination we have measured the production of chloroform in the upper soil from different terrestrial systems. Field measurements of chloroform in top soil air were used as production indicators. The production was however not evenly distributed at any scale. The ecosystems seem to have quite different net-productions of chloroform from very low in grassland to very high in some coniferous forests. Within the forest ecosystem we found large variation in chloroform concentrations depending on vegetation. In beech forest we found the lowest values, somewhat higher in an open pine forest, but the highest concentrations were detected in spruce forest without any vegetation beneath. Within this ecotype, it appeared that the variation was also large; hot spots with 2-4 decades higher production than the surrounding area. These hot spots were not in any way visually different from the surroundings and were of variable size from 3 to 20 meters in diameter. Besides this, measurements within a seemingly homogenous hot spot showed that there was still high

  16. How Similar Are Protein Folding and Protein Binding Nuclei? Examination of Vibrational Motions of Energy Hot Spots and Conserved Residues

    OpenAIRE

    Haliloglu, Turkan; Keskin, Ozlem; Ma, Buyong; Nussinov, Ruth

    2004-01-01

    The underlying physico-chemical principles of the interactions between domains in protein folding are similar to those between protein molecules in binding. Here we show that conserved residues and experimental hot spots at intermolecular binding interfaces overlap residues that vibrate with high frequencies. Similarly, conserved residues and hot spots are found in protein cores and are also observed to vibrate with high frequencies. In both cases, these residues contribute significantly to t...

  17. Predicting hot spots in protein interfaces based on protrusion index, pseudo hydrophobicity and electron-ion interaction pseudopotential features

    Science.gov (United States)

    Xia, Junfeng; Yue, Zhenyu; Di, Yunqiang; Zhu, Xiaolei; Zheng, Chun-Hou

    2016-01-01

    The identification of hot spots, a small subset of protein interfaces that accounts for the majority of binding free energy, is becoming more important for the research of drug design and cancer development. Based on our previous methods (APIS and KFC2), here we proposed a novel hot spot prediction method. For each hot spot residue, we firstly constructed a wide variety of 108 sequence, structural, and neighborhood features to characterize potential hot spot residues, including conventional ones and new one (pseudo hydrophobicity) exploited in this study. We then selected 3 top-ranking features that contribute the most in the classification by a two-step feature selection process consisting of minimal-redundancy-maximal-relevance algorithm and an exhaustive search method. We used support vector machines to build our final prediction model. When testing our model on an independent test set, our method showed the highest F1-score of 0.70 and MCC of 0.46 comparing with the existing state-of-the-art hot spot prediction methods. Our results indicate that these features are more effective than the conventional features considered previously, and that the combination of our and traditional features may support the creation of a discriminative feature set for efficient prediction of hot spots in protein interfaces. PMID:26934646

  18. Process window and defect monitoring using high-throughput e-beam inspection guided by computational hot spot detection

    Science.gov (United States)

    Wang, Fei; Zhang, Pengcheng; Fang, Wei; Liu, Kevin; Jau, Jack; Wang, Lester; Wan, Alex; Hunsche, Stefan; Halder, Sandip; Leray, Philippe

    2016-03-01

    As design rules for leading edge devices have shrunk to 1x nm size and below, device patterns have become sensitive to sub-10nm size defects. Additionally, defectivity and yield are now increasingly dominated by systematic patterning defects. A method for identifying and inspecting these hot spot (HS) locations is necessary for both technology development and High Volume Manufacturing (HVM). In order to achieve sufficient statistical significance across the wafer for a specific product and layer, a guided, high-speed e-beam inspection system is needed to cover a significant amount of high-volume hot spot locations for process window monitoring. In this paper, we explore the capabilities of a novel, highthroughput e-beam hot spot inspection tool, SkyScanTM 5000, on a 10nm back-end-of-line (BEOL) wafer patterned using a triple lithography-etch process. ASML's high-resolution, design-aware computational hot spot inspection is used to identify relevant hot spot locations, including overlay-sensitive patterns. We guide the e-beam tool to these Points of Interest (POI) and obtain experimental data from inspection of 430k wafer locations. The large amount of data allows detection of wafer-level and intra-field defect signatures for a large number of hot spot patterns.

  19. Hot spot mitigation in microprocessors by application of single phase microchannel heat sink and microprocessor floor planning

    Science.gov (United States)

    Chauhan, Anjali

    Poor thermal management in high frequency microprocessors results in thermal and mechanical stresses in the chip due to leakage losses, occurrence of hot spots and large temperature gradients. A micro-fluidics based cooling scheme of single phase microchannel heat sinks is found to be most promising cooling solution. Microchannel heat sinks have high cooling capability because of its high surface area to volume ratio and high heat transfer coefficient. Besides the fluid flow, heat transfer mechanism in microchannel heat sinks is affected by its installation on the microprocessor chip. Since microchannel heat sinks are capable of reducing only the average temperature rise of the microprocessor chip, technique of microprocessor floor planning can be applied to reduce hot spot temperature, mitigate multiple hot spots and reduce large temperature gradients on the surface of microprocessor chip. In this study, adequate installation of the microchannel heat sink on the processor chip has been proposed to extract maximum heat from the device. Microprocessor floor planning has also been explored to obtain an optimum chip floor plan on grounds of low performance penalty, low hot spot temperature and minimum number hot spots. The dependence of maximum hot spot temperature of the chip on pressure gradient across the microchannels has also been discussed.

  20. Airborne Remote Sensing of a Biological Hot Spot in the Southeastern Bering Sea

    Directory of Open Access Journals (Sweden)

    Michael F. Sigler

    2011-03-01

    Full Text Available Intense, ephemeral foraging events within localized hot spots represent important trophic transfers to top predators in marine ecosystems, though the spatial extent and temporal overlap of predators and prey are difficult to observe using traditional methods. The southeastern Bering Sea has high marine productivity along the shelf break, especially near marine canyons. At a hot spot located near Bering Canyon, we observed three foraging events over a 12 day period in June 2005. These were located by aerial surveys, quantified by airborne lidar and visual counts, and characterized by ship-based acoustics and net catches. Because of the high density of seabirds, the events could be seen in images from space-based synthetic aperture radar. The events developed at the shelf slope, adjacent to passes between the Aleutian Islands, persisted for 1 to 8 days, then abruptly disappeared. Build-up and break down of the events occurred on 24 hr time scales, and diameters ranged from 10 to 20 km. These events comprised large concentrations of euphausiids, copepods, herring, other small pelagic fishes, humpback whales, Dall’s porpoise, short-tailed shearwaters, northern fulmars, and other pelagic seabirds. The lidar and acoustic remote sensing data demonstrated that prey densities inside the events were several times higher than those outside, indicating the importance of including events in forage fish surveys. This implies a need for either very intensive traditional surveys covering large expanses or for adaptive surveys guided by remote sensing. To our knowledge, this is the first time that an Alaskan hot spot was monitored with the combination of airborne and satellite remote sensing.

  1. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, pareas that showed high and low significant regulating and cultural ES clusters are similar. The spatial distribution of these clusters is very high, which may be attributed to

  2. WiFi hot spot superdistribution : a profit scheme for WiFi access distribution

    OpenAIRE

    Fritsch, Lothar

    2005-01-01

    The wide-area deployment of WiFi hot spots challenges IP access providers. While new profit models are sought after by them, profitability as well as logistics for large-scale deployment of 802.11 wireless technology are still to be proven. Expenditure for hardware, locations, maintenance, connectivity, marketing, billing and customer care must be considered. Even for large carriers with infrastructure, the deployment of a large-scale WiFi infrastructure may be risky. This paper proposes a mu...

  3. Detection of spatial hot spots and variation for the neon flying squid Ommastrephes bartramii resources in the northwest Pacific Ocean

    Science.gov (United States)

    Feng, Yongjiu; Chen, Xinjun; Liu, Yan

    2016-08-01

    With the increasing effects of global climate change and fishing activities, the spatial distribution of the neon flying squid (Ommastrephes bartramii) is changing in the traditional fishing ground of 150°-160°E and 38°-45°N in the northwest Pacific Ocean. This research aims to identify the spatial hot and cold spots (i.e. spatial clusters) of O. bartramii to reveal its spatial structure using commercial fishery data from 2007 to 2010 collected by Chinese mainland squid-jigging fleets. A relatively strongly-clustered distribution for O. bartramii was observed using an exploratory spatial data analysis (ESDA) method. The results show two hot spots and one cold spot in 2007 while only one hot and one cold spots were identified each year from 2008 to 2010. The hot and cold spots in 2007 occupied 8.2% and 5.6% of the study area, respectively; these percentages for hot and cold spot areas were 5.8% and 3.1% in 2008, 10.2% and 2.9% in 2009, and 16.4% and 11.9% in 2010, respectively. Nearly half (>45%) of the squid from 2007 to 2009 reported by Chinese fleets were caught in hot spot areas while this percentage reached its peak at 68.8% in 2010, indicating that the hot spot areas are central fishing grounds. A further change analysis shows the area centered at 156°E/43.5°N was persistent as a hot spot over the whole period from 2007 to 2010. Furthermore, the hot spots were mainly identified in areas with sea surface temperature (SST) in the range of 15-20°C around warm Kuroshio Currents as well as with the chlorophyll-a (chl-a) concentration above 0.3 mg/m3. The outcome of this research improves our understanding of spatiotemporal hotspots and its variation for O. bartramii and is useful for sustainable exploitation, assessment, and management of this squid.

  4. A high resolution view of the jet termination shock in a hot spot of the nearby radio galaxy Pictor A: implications for X-ray models of radio galaxy hot spots

    CERN Document Server

    Tingay, S J; Brunetti, G; Bondi, M

    2008-01-01

    Images made with the VLBA have resolved the region in a nearby radio galaxy, Pictor A, where the relativistic jet that originates at the nucleus terminates in an interaction with the intergalactic medium, a so-called radio galaxy hot spot. This image provides the highest spatial resolution view of such an object to date (16 pc), more than three times better than previous VLBI observations of similar objects. The north-west Pictor A hot spot is resolved into a complex set of compact components, seen to coincide with the bright part of the hot spot imaged at arcsecond-scale resolution with the VLA. In addition to a comparison with VLA data, we compare our VLBA results with data from the HST and Chandra telescopes, as well as new Spitzer data. The presence of pc-scale components in the hot spot, identifying regions containing strong shocks in the fluid flow, leads us to explore the suggestion that they represent sites of synchrotron X-ray production, contributing to the integrated X-ray flux of the hot spot, alo...

  5. Space and time resolved observations of hot spots dynamics in a vacuum spark discharge

    International Nuclear Information System (INIS)

    Experimental observations of the plasma formations in a vacuum spark discharge are presented. A low power Nd:YAG laser pulse incident onto a titanium cathode initiates the discharge. The evolution of the titanium plasma electron density and temperature is followed both in the visible and the soft X-ray part of the spectrum. The former uses a novel micro holographic interferometric technique permitting a spatial resolution better than 20 μm. The probing beam is a 6 ns frequency doubled Nd:YAG laser. The latter emission is resolved using a number of different methods. The spatial information is derived from a 1 ns multi framing camera X-ray camera which projects the plasma image using four different slit wire pinhole images and six pinhole images, each aperture being filtered differently. The temporal evolution of the emission of each discharge is followed using several silicon PIN diodes. The x-ray spectrum is unfolded from the filter and detector response and interpreted using a collisional radiative package. The hot spots are seen to form in a submillimeter pinch stemming from the incident laser focus which has a life time about 20 ns. The hot spots are much shorter events, reaching substantially higher densities, but involve only part of the line density of the pinch column. (author). 4 figs., 8 refs

  6. Analysis and Visualization for Hot Spot Based Route Recommendation Using Short-Dated Taxi GPS Traces

    Directory of Open Access Journals (Sweden)

    Ying Shen

    2015-04-01

    Full Text Available Taxi GPS traces, which contain a great deal of valuable information as regards to human mobility and city traffic, can be extracted to improve the quality of our lives. Since the method of visualized analysis is believed to be an effective way to present information vividly, we develop our analysis and visualization method based on a city’s short-dated taxi GPS traces, which can provide recommendation to help cruising taxi drivers to find potential passengers with optimal routes. With our approach, hot spots for loading and unloading passenger(s are extracted using an improved DBSCAN algorithm after data preprocessing including cleaning and filtering. Then, this paper describes the start-end point-based similar trajectory method to get coarse-level trajectories clusters, together with the density-based ε distance trajectory clustering algorithm to identify recommended potential routes. A weighted tree is defined including such factors as driving time, velocity, distance and endpoint attractiveness for optimal route evaluation from vacant to occupied hot spots. An example is presented to show the effectiveness of our visualization method.

  7. Possible hot spots excited by the relativistic jets of Cygnus X-3

    CERN Document Server

    Martí, J; Garrido, J L; Luque-Escamilla, P; Paredes, J M

    2005-01-01

    We present the results of a deep search for associated radio features in the vicinity of the microquasar Cygnus X-3. The motivation behind is to find out evidence for interaction between its relativistic jets and the surrounding interstellar medium, which could eventually allow us to perform calorimetry of the total energy released by this microquasar during its flaring lifetime. Remarkably, two radio sources with mJy emission level at centimeter wavelengths have been detected in excellent alignment with the position angle of the inner radio jets. We propose that these objects could be the hot spots where the relativitic outflow collides with the ambient gas in analogy with Fanaroff-Riley II radio galaxies. These candidate hot spots are within a few arc-minutes of Cygnus X-3 and, if physically related, the full linear extent of the jet would reach tens of parsecs. We discuss here the evidence currently available to support this hypothesis based on both archival data and our own observations.

  8. Hot spots and future directions of research on the neuroprotective effects of nimodipine

    Institute of Scientific and Technical Information of China (English)

    Runhui Li

    2014-01-01

    Calcium antagonists are widely used in the clinical treatment of ischemic cerebrovascular disease because of their vascular and neuroprotective effects. Nimodipine, a typical calcium antagonist, can cross the blood-brain barrier and act selectively at neurons and blood vessels of target tis-sues, thus exerting neuroprotective effects. The aim of the present study was to explore the hot spots and future trends of research on the neuroprotective effects of nimodipine. We retrieved 425 articles on the neuroprotective effects of nimodipine that were indexed in the Web of the Science database between 2000 and 2014. The retrieved articles were analyzed using document analysis reporting and the derived information function in the Web of Science, and the infor-mation visualization software CiteSpace III. The reference co-citation network was plotted, and the high frequency key words in these publications were used to analyze the research fronts and development trends for nimodipine neuroprotection. According to these co-citation clusters, the research front of nimodipine neuroprotection is the use of randomized controlled trials to study nimodipine intervention of subarachnoid hemorrhage. Using time zone view analysis on hot spots labeled with a key word, the areas of interest in the ifeld of nimodipine neuroprotection are nimodipine pharmacology and therapeutics, blood-brain barrier, trials, and anti-angiospasm.

  9. Sensitivity of inertial confinement fusion hot spot properties to the deuterium-tritium fuel adiabat

    Energy Technology Data Exchange (ETDEWEB)

    Melvin, J.; Lim, H.; Rana, V.; Glimm, J. [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600 (United States); Cheng, B.; Sharp, D. H.; Wilson, D. C. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2015-02-15

    We determine the dependence of key Inertial Confinement Fusion (ICF) hot spot simulation properties on the deuterium-tritium fuel adiabat, here modified by addition of energy to the cold shell. Variation of this parameter reduces the simulation to experiment discrepancy in some, but not all, experimentally inferred quantities. Using simulations with radiation drives tuned to match experimental shots N120321 and N120405 from the National Ignition Campaign (NIC), we carry out sets of simulations with varying amounts of added entropy and examine the sensitivities of important experimental quantities. Neutron yields, burn widths, hot spot densities, and pressures follow a trend approaching their experimentally inferred quantities. Ion temperatures and areal densities are sensitive to the adiabat changes, but do not necessarily converge to their experimental quantities with the added entropy. This suggests that a modification to the simulation adiabat is one of, but not the only explanation of the observed simulation to experiment discrepancies. In addition, we use a theoretical model to predict 3D mix and observe a slight trend toward less mixing as the entropy is enhanced. Instantaneous quantities are assessed at the time of maximum neutron production, determined dynamically within each simulation. These trends contribute to ICF science, as an effort to understand the NIC simulation to experiment discrepancy, and in their relation to the high foot experiments, which features a higher adiabat in the experimental design and an improved neutron yield in the experimental results.

  10. VLBI observations of 10 CSO candidates: expansion velocities of hot spots

    CERN Document Server

    An, Tao; Yang, Jun; Taylor, Gregory B; Hong, Xiaoyu; Baan, Willem A; Liu, Xiang; Wang, Min; Zhang, Hongbo; Wang, Weihua; Chen, Xi; Cui, Lang; Hao, Longfei; Zhu, Xinying

    2011-01-01

    Observations of ten Compact Symmetric Objects ({\\rm CSO}) candidates have been made with the Very Long Baseline Array at 8.4 GHz in 2005 and with a combined Chinese and European VLBI array at 8.4 GHz in 2009. The 2009 observations incorporate for the first time the two new Chinese telescopes at Miyun and Kunming for international astrophysical observations. The observational data, in combination with archival VLBA data from previous epochs, have been used to derive the proper motions of the VLBI components. Because of the long time baseline of $\\sim$16 years of the VLBI data sets, the expansion velocities of the hot spots can be measured at an accuracy as high as $\\sim$1.3 $\\mu$as yr$^{-1}$. Six of the ten sources are identified as CSOs with a typical double or triple morphology on the basis of both spectral index maps and their mirror-symmetry of proper motions of the terminal hot spots. The compact double source J1324+4048 is also identified as a CSO candidate. Among the three remaining sources, J1756+5748 ...

  11. Nuclear star formation in the hot-spot galaxy NGC2903

    CERN Document Server

    Alonso-Herrero, A; Knapen, J H

    2000-01-01

    We present high-resolution near-infrared imaging obtained using adaptive optics and HST/NICMOS, and ground-based spectroscopy of the hot-spot galaxy NGC2903. Our near-infrared resolution imaging enables us to resolve the infrared hot spots into individual young stellar clusters or groups of these. The spatial distribution of the stellar clusters is not coincident with that of the bright HII regions, as revealed by the HST/NICMOS Pa_alpha image. Overall, the circumnuclear star formation in NGC2903 shows a ring-like morphology with an approximate diameter of 625pc. The SF properties of the stellar clusters and HII regions have been studied using the photometric and spectroscopic information in conjunction with evolutionary synthesis models. The population of bright stellar clusters shows a very narrow range of ages, 4-7 X 10^6 yr after the peak of star formation, or absolute ages 6.5-9.5 X 10^6yr (for the assumed short-duration Gaussian bursts), and luminosities similar to the clusters found in the Antennae int...

  12. Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.

    Science.gov (United States)

    Rawson, Jonathan M O; Landman, Sean R; Reilly, Cavan S; Bonnac, Laurent; Patterson, Steven E; Mansky, Louis M

    2015-11-01

    Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity.

  13. HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering.

    Science.gov (United States)

    Bendl, Jaroslav; Stourac, Jan; Sebestova, Eva; Vavra, Ondrej; Musil, Milos; Brezovsky, Jan; Damborsky, Jiri

    2016-07-01

    HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins' stability, catalytic activity, substrate specificity and enantioselectivity. The server integrates sequence, structural and evolutionary information obtained from 3 databases and 20 computational tools. Users are guided through the processes of selecting hot spots using four different protein engineering strategies and optimizing the resulting library's size by narrowing down a set of substitutions at individual randomized positions. The only required input is a query protein structure. The results of the calculations are mapped onto the protein's structure and visualized with a JSmol applet. HotSpot Wizard lists annotated residues suitable for mutagenesis and can automatically design appropriate codons for each implemented strategy. Overall, HotSpot Wizard provides comprehensive annotations of protein structures and assists protein engineers with the rational design of site-specific mutations and focused libraries. It is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard.

  14. KFC2: a knowledge-based hot spot prediction method based on interface solvation, atomic density, and plasticity features.

    Science.gov (United States)

    Zhu, Xiaolei; Mitchell, Julie C

    2011-09-01

    Hot spots constitute a small fraction of protein-protein interface residues, yet they account for a large fraction of the binding affinity. Based on our previous method (KFC), we present two new methods (KFC2a and KFC2b) that outperform other methods at hot spot prediction. A number of improvements were made in developing these new methods. First, we created a training data set that contained a similar number of hot spot and non-hot spot residues. In addition, we generated 47 different features, and different numbers of features were used to train the models to avoid over-fitting. Finally, two feature combinations were selected: One (used in KFC2a) is composed of eight features that are mainly related to solvent accessible surface area and local plasticity; the other (KFC2b) is composed of seven features, only two of which are identical to those used in KFC2a. The two models were built using support vector machines (SVM). The two KFC2 models were then tested on a mixed independent test set, and compared with other methods such as Robetta, FOLDEF, HotPoint, MINERVA, and KFC. KFC2a showed the highest predictive accuracy for hot spot residues (True Positive Rate: TPR = 0.85); however, the false positive rate was somewhat higher than for other models. KFC2b showed the best predictive accuracy for hot spot residues (True Positive Rate: TPR = 0.62) among all methods other than KFC2a, and the False Positive Rate (FPR = 0.15) was comparable with other highly predictive methods.

  15. XMM-Newton observations of the hot spot galaxy NGC 2903

    CERN Document Server

    Perez-Ramirez, D; Ebrero, J; Leon, S

    2010-01-01

    We report on the first deeper X-ray broad-band observation of the hot spot galaxy NGC 2903 obtained with XMM-Newton. X-ray imaging and spectra of the spiral barred galaxy NGC 2903 were obtained from recently available XMM-Newton archival data in order to study its X-ray population and the conditions of the hot gas in its central region. We investigate the spectral properties for the discrete point-source population and give first estimations of their X-ray spectral parameters. By analysing the RGS spectra, we derive temperature and abundances for the hot gas located in its central region. A total of 6 X-ray point sources (4 of them ULX candidates) were detected in the energy range of 0.3-10.0 keV located within the galaxy D25 optical disk. 3 out of these sources are detected for the first time, and one of them, XMM-NGC2903 X2 with luminosity larger than 10^39 erg/s. After fitting three different models, we were able to estimate their luminosities which are compatible with binaries with a compact object in the...

  16. Multifocal hot spots demonstrated by whole-body 131I scintigraphy and SPECT/CT after transaxillary endoscopic thyroidectomy.

    Science.gov (United States)

    Kim, Ho Seong; Kim, Seok Hwi; Kim, Jung Han; Kim, Byung-Tae; Lee, Kyung-Han

    2015-03-01

    A 35-year-old woman received open thyroidectomy for a thyroid nodule that was confirmed as papillary carcinoma. Whole-body 131I scintigraphy during thyroid ablation demonstrated high uptake in the thyroid bed and multiple focal hot spots in the thorax. SPECT/CT localized the hot spots to the right chest wall and axilla, as well as to the left chest wall. The surgeon recognized these sites to concur with the transaxillary tract used during endoscopic thyroidectomy for nodular hyperplasia 8 years previously. Thus, this case illustrates how thyroidal tissue fragments seeded during endoscopic thyroidectomy can be mistaken for thyroid cancer metastasis on 131I scintigraphy.

  17. Surface micro-topography causes hot spots of biogeochemical activity in wetland systems: A virtual modeling experiment

    Science.gov (United States)

    Frei, S.; Knorr, K. H.; Peiffer, S.; Fleckenstein, J. H.

    2012-12-01

    Wetlands provide important ecohydrological services by regulating fluxes of nutrients and pollutants to receiving waters, which can in turn mitigate adverse effects on water quality. Turnover of redox-sensitive solutes in wetlands has been shown to take place in distinct spatial and temporal patterns, commonly referred to as hot spots and hot moments. Despite the importance of such patterns for solute fluxes the mechanistic understanding of their formation is still weak and their existence is often explained by variations in soil properties and diffusive transport only. Here we show that surface micro-topography in wetlands can cause the formation of biogeochemical hot spots solely by the advective redistribution of infiltrating water as a result of complex subsurface flow patterns. Surface and subsurface flows are simulated for an idealized section of a riparian wetland using a fully integrated numerical code for coupled surface-subsurface systems. Biogeochemical processes and transport along advective subsurface flow paths are simulated kinetically using the biogeochemical code PHREEQC. Distinct patterns of biogeochemical activity (expressed as reaction rates) develop in response to micro-topography induced subsurface flow patterns. Simulated vertical pore water profiles for various redox-sensitive species resemble profiles observed in the field. This mechanistic explanation of hot spot formation complements the more static explanations that relate hot spots solely to spatial variability in soil characteristics and can account for spatial as well as temporal variability of biogeochemical activity, which is needed to assess future changes in the biogeochemical turnover of wetland systems.

  18. Thermally smart characteristics of nanofluids in parallel microchannel systems to mitigate hot spots in MEMS

    CERN Document Server

    Maganti, Lakshmi Sirisha; Sundararajan, T; Das, Sarit K

    2016-01-01

    Mitigation of hot spots in MEMS employing in situ microchannel systems requires a comprehensive picture of the maldistribution of the working fluid and uniformity of cooling within the same. In this article, detailed simulations employing parallel micro channel systems with specialized manifold-channel configurations i.e. U, I and Z have been performed. Eulerian Lagrangian Discrete Phase Model and Effective Property Model with water and alumina water nanofluid as working fluids have been employed. The distributions of the dispersed particulate phase and continuous phase have been observed to be, in general, different from the flow distribution and this has been found to be strongly dependent on the flow configuration. Particle maldistribution has been conclusively shown to be influenced by various migration and diffusive phenomena like Stokesian drag, Brownian motion, thermophoretic drift, etc. To understand the uniformity of cooling within the device, which is of importance in real time scenario, an appropri...

  19. Hot and cold spots counts as probes of non-Gaussianity in the CMB

    CERN Document Server

    Chingangbam, Pravabati; Yogendran, K P; van de Weygaert, Rien

    2012-01-01

    We introduce the numbers of hot and cold spots, $n_h$ and $n_c$, of excursion sets of the CMB temperature anisotropy maps as statistical observables that can discriminate different non-Gaussian models. We numerically compute them from simulations of non-Gaussian CMB temperature fluctuation maps. The first kind of non-Gaussian model we study is the local type primordial non-Gaussianity. The second kind of models have some specific form of the probability distribution function from which the temperature fluctuation value at each pixel is drawn, obtained using HEALPIX. We find the characteristic non-Gaussian deviation shapes of $n_h$ and $n_c$, which is distinct for each of the models under consideration. We further demonstrate that $n_h$ and $n_c$ carry additional information compared to the genus, which is just their linear combination, making them valuable additions to the Minkowski Functionals in constraining non-Gaussianity.

  20. Enhancement of electron hot spot relaxation in photoexcited plasmonic structures by thermal diffusion

    CERN Document Server

    Spitzer, F; Belotelov, V I; Vondran, J; Akimov, I A; Kasture, S; Achanta, V G; Yakovlev, D R; Bayer, M

    2016-01-01

    We demonstrate that in confined plasmonic metal structures subject to ultra-fast laser excitation electron thermal diffusion can provide relaxation faster than the energy transfer to the lattice. This relaxation occurs due to excitation of nanometer-sized hot spots in the confined structure and the sensitivity of its optical parameters to the perturbation in these regions. Both factors become essential when the plasmonic resonance condition is met for both excitation and detection. A pump-probe experiment on plasmonic gold lattices shows sub-picosecond relaxation with the characteristic times well-described by a two-temperature model. The results suggest that dynamical optical response in plasmonic structures can be tuned by selection of the structural geometry as well as the choice of wavelength and polarization of the excitation and detection light.

  1. Magnetic quadrupoles lens for hot spot proton imaging in inertial confinement fusion

    Science.gov (United States)

    Teng, J.; Gu, Y. Q.; Chen, J.; Zhu, B.; Zhang, B.; Zhang, T. K.; Tan, F.; Hong, W.; Zhang, B. H.; Wang, X. Q.

    2016-08-01

    Imaging of DD-produced protons from an implosion hot spot region by miniature permanent magnetic quadrupole (PMQ) lens is proposed. Corresponding object-image relation is deduced and an adjust method for this imaging system is discussed. Ideal point-to-point imaging demands a monoenergetic proton source; nevertheless, we proved that the blur of image induced by proton energy spread is a second order effect therefore controllable. A proton imaging system based on miniature PMQ lens is designed for 2.8 MeV DD-protons and the adjust method in case of proton energy shift is proposed. The spatial resolution of this system is better than 10 μm when proton yield is above 109 and the spectra width is within 10%.

  2. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, p<0.001). The Z score of providing services (0.096±2.239) were significantly higher than the total (0.093±2.045), cultural (0.080±1.979) and regulating (0.076±1.961). These

  3. Mapping the energy distribution of SERRS hot spots from anti-Stokes to Stokes intensity ratios.

    Science.gov (United States)

    dos Santos, Diego P; Temperini, Marcia L A; Brolo, Alexandre G

    2012-08-15

    The anomalies in the anti-Stokes to Stokes intensity ratios in single-molecule surface-enhanced resonance Raman scattering were investigated. Brilliant green and crystal violet dyes were the molecular probes, and the experiments were carried out on an electrochemically activated Ag surface. The results allowed new insights into the origin of these anomalies and led to a new method to confirm the single-molecule regime in surface-enhanced Raman scattering. Moreover, a methodology to estimate the distribution of resonance energies that contributed to the imbalance in the anti-Stokes to Stokes intensity ratios at the electromagnetic hot spots was proposed. This method allowed the local plasmonic resonance energies on the metallic surface to be spatially mapped. PMID:22804227

  4. Is the Juan Fernandez Ridge (nazca Plate) a Deep-Mantle Hot SPOT Trail?

    Science.gov (United States)

    Lara, L. E.; Selles, D.; Díaz, A.; Piña-Gauthier, M.

    2011-12-01

    The Juan Fernández Ridge on the oceanic Nazca plate is thought to be a classic hot spot trail because of the apparent westward rejuvenation of the eruptive ages. Geochronological data is still scarce to prove this is the case, and other hypothesis should be taken into account. There are a few constrains, like the ca. 9 Ma Ar-Ar age of the O'Higgins seamount (115 km from the Chile-Perú trench), published K-Ar ages of ca. 3-4 Ma in Robinson Crusoe island (580 km from the trench) and ca. 1 Ma in Alejandro Selkirk (180 km further west). New reconnaissance K-Ar ages in Robinson Crusoe yield ca. 1-3 Ma, which partially overlap with the age of Alejandro Selkirk, breaking the expected age progression given that the Nazca plate moves eastwards at ca. 6-8 cm/yr. New geological mapping also shows a sharp unconformity between the older, strongly altered sequences and more recent, post-erosional volcanic piles, where only the vent facies have disappeared. A fixed deep-mantle plume origin for Pacific hot spots has been widely debated and concurrent phenomena arose as a possible explanation for non-linear age progressions and/or long-lived volcanic activity. In fact, intraplate regional tectonics, plume displacement, and mantle heterogeneities could be the main factor of the ridge architecture or the mask for a first-order linear trend. An ongoing mapping and dating effort is aimed to understand the evolution of the Juan Fernández Ridge, testing the main hypothesis. Fondecyt grant 110966 is acknowledged for financial support.

  5. Monolithic nanoporous gold disks with large surface area and high-density plasmonic hot-spots

    Science.gov (United States)

    Zhao, Fusheng; Zeng, Jianbo; Arnob, Md Masud Parvez; Santos, Greggy M.; Shih, Wei-Chuan

    2015-03-01

    Plasmonic metal nanostructures have shown great potential in sensing, photovoltaics, imaging and biomedicine, principally due to enhancement of the local electric field by light-excited surface plasmons, the collective oscillation of conduction band electrons. Thin films of nanoporous gold have received a great deal of interest due to the unique 3- dimensional bicontinuous nanostructures with high specific surface area. However, in the form of semi-infinite thin films, nanoporous gold exhibits weak plasmonic extinction and little tunability in the plasmon resonance, because the pore size is much smaller than the wavelength of light. Here we show that by making nanoporous gold in the form of disks of sub-wavelength diameter and sub-100 nm thickness, these limitations can be overcome. Nanoporous gold disks (NPGDs) not only possess large specific surface area but also high-density, internal plasmonic "hot-spots" with impressive electric field enhancement, which greatly promotes plasmon-matter interaction as evidenced by spectral shifts in the surface plasmon resonance. In addition, the plasmonic resonance of NPGD can be easily tuned from 900 to 1850 nm by changing the disk diameter from 300 to 700 nm. The coupling between external and internal nanoarchitecture provides a potential design dimension for plasmonic engineering. The synergy of large specific surface area, high-density hot spots, and tunable plasmonics would profoundly impact applications where plasmonic nanoparticles and non-plasmonic mesoporous nanoparticles are currently employed, e.g., in in-vitro and in-vivo biosensing, molecular imaging, photothermal contrast agents, and molecular cargos.

  6. Chain of impact of the development of hot spots and hot rubbing in disk brakes of passenger cars; Wirkungskette der Entstehung von Hotspots und Heissrubbeln in Pkw-Scheibenbremsen

    Energy Technology Data Exchange (ETDEWEB)

    Sarda, Angelo

    2009-07-01

    Aspects coupled with brake comfort represent challenges with the development of brake systems. During the brake process, so-called hot spots on the surface of brake disks are developed under certain conditions. These hot spots result in an irregular thermal expansion and deformation of the brake disk. This results in vibrations impacting the comfort and being known as 'hot rubbing'. The author of the contribution under consideration describes the most important results from extensive benchmark tests and supplies experimentally secured realizations to the chain of impact of the development of hot spots and 'hot rubbing' in a disc brake.

  7. Standard Test Method for Hot Spot Protection Testing of Photovoltaic Modules

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This test method provides a procedure to determine the ability of a photovoltaic (PV) module to endure the long-term effects of periodic “hot spot” heating associated with common fault conditions such as severely cracked or mismatched cells, single-point open circuit failures (for example, interconnect failures), partial (or non-uniform) shadowing or soiling. Such effects typically include solder melting or deterioration of the encapsulation, but in severe cases could progress to combustion of the PV module and surrounding materials. 1.2 There are two ways that cells can cause a hot spot problem; either by having a high resistance so that there is a large resistance in the circuit, or by having a low resistance area (shunt) such that there is a high-current flow in a localized region. This test method selects cells of both types to be stressed. 1.3 This test method does not establish pass or fail levels. The determination of acceptable or unacceptable results is beyond the scope of this test method....

  8. Study on the resistance spot welding technology of 22MnMoB hot stamping quenched steel

    Institute of Scientific and Technical Information of China (English)

    Feng Yi; Ma Mingtu; Hua Fuan; Zhang Junping; Song Leifeng; Jin Qingsheng

    2014-01-01

    In this paper,the spot welding technology of a new kind of 22MnMoB hot stamping quenched steel sheet was systematically studied by power frequency spot welder. Through a series of technology and test exper-iments,we have obtained the optimal spot welding technological parameter condition. According to the results, the relations among spot welding technological parameter,welding nugget,mechanical property and fracture mode were discussed. The effects of all the welding parameters such as welding current,welding time and elec-trode force on the quality of joint can be boiled down to one thing-the diameter of welding nugget. The experi-mental results showed that welding nugget diameter determines the mechanical property of spot welding joint and the relation between welding nugget diameter and the mechanical property of joint presents a kind of linear mathematic representation. There are two typical fracture models of 22MnMoB hot stamping quenched steel sheet,i.e.,interfacial fracture and nugget pullout. Other than mild steel or normal high strength steel,in the shearing tensile test,hot stamping quenched steel has a great tendency to fail in interfacial mode due to the ef-fects of high strength matrix structure,welding soft zone and the porosity level of fusion zone.

  9. Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo.

    Science.gov (United States)

    Tchurikov, Nickolai A; Yudkin, Dmitry V; Gorbacheva, Maria A; Kulemzina, Anastasia I; Grischenko, Irina V; Fedoseeva, Daria M; Sosin, Dmitri V; Kravatsky, Yuri V; Kretova, Olga V

    2016-01-01

    Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3-6). Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics. PMID:27160357

  10. Localization of Temperature Using Plasmonic Hot Spots in Metal Nanostructures: The Nano-Optical Antenna Approach and Fano Effect

    CERN Document Server

    Khorashad, Larousse Khosravi; Valentine, Jason; Govorov, Alexander O

    2016-01-01

    It is challenging to strongly localize temperature in small volumes because heat transfer is a diffusive process. Here we show how to overcome this limitation using electrodynamic hot spots and interference effects in the regime of continuous-wave (CW) excitation. We introduce a set of figures of merit for the localization of temperature and for the efficiency of the plasmonic photo-thermal effect. Our calculations show that the temperature localization in a trimer nanoparticle assembly is a complex function of the geometry and sizes. Large nanoparticles in the trimer play the role of the nano-optical antenna whereas the small nanoparticle in the plasmonic hot spot acts as a nano-heater. Under the peculiar conditions, the temperature increase inside a nanoparticle trimer can be localized in a hot spot region at the small heater nanoparticle and, in this way, a thermal hot spot can be realized. However, the overall power efficiency of temperature generation in this trimer is much smaller than that of a single ...

  11. The anatomy of a radio source hot spot : Very large baseline array imaging of 3C 205

    NARCIS (Netherlands)

    Lonsdale, CJ; Barthel, PD

    1998-01-01

    Total intensity and linear polarization Very Long Baseline Array (VLBA) images of the high-redshift quasar 3C 205 at a wavelength of 18 cm reveal a complex curved hot-spot structure with polarization percentages frequently as high as 70%. A one-sided jet is detected emerging from the central compone

  12. 40 CFR 93.116 - Criteria and procedures: Localized CO, PM10, and PM2.5 violations (hot-spots).

    Science.gov (United States)

    2010-07-01

    ..., PM10, and PM2.5 violations (hot-spots). 93.116 Section 93.116 Protection of Environment ENVIRONMENTAL....116 Criteria and procedures: Localized CO, PM10, and PM2.5 violations (hot-spots). (a) This paragraph.../or PM2.5 violations, increase the frequency or severity of any existing CO, PM10, and/or...

  13. Hot spot formation of chloroform in forest soils caused pollution of groundwater

    Science.gov (United States)

    Jacobsen, Ole S.; Albers, Christian N.; Laier, Troels; Hunkeler, Daniel

    2015-04-01

    High concentration of chloroform in groundwater is usually attributed to anthropogenic input, but we have found that the groundwater beneath some pristine areas contained chloroform from 1 - 10 µg/L. Groundwater containing chloroform that exceeds 1 µg/L could not be used for drinking water according to Danish regulations. The strict demands on groundwater quality may have to be taken into account when decisions are made regarding the change of land use in order to protect major recharge areas from pollution with nitrate and pesticides resulting from high-yield agriculture production. The terrestrial environment and especially hot spots in forest soils seem to be important contributors to apparent pollution of groundwater with chloroform. We performed a field study to investigate concentration and fluxes of chloroform to the groundwater from in four coniferous forests in order to increase knowledge on the hot spot formation and fate of natural chloroform. We investigated four stations over a period of several years in order to measure the net-formation of chloroform. Field measurements soil air concentrations of chloroform were monitored in five soil profiles down to the groundwater table. Meteorological data were recorded at all stations In the hotspots up to 120 ppbv was found in soil air under the spruce forest, to be compared to an ambient atmospheric concentration of 0.02 ppbv. The concentration of chloroform in soil air showed seasonal variation with a maximum in August-September. The chloroform concentration decreased with depth in all profiles during the summer half-year to about 20 % of concentration in the production layer. However, the concentration is still high enough to give an equilibrium concentration in the upper groundwater of 1-10 µg/L. Stable carbon isotopic analyses of chloroform from the uppermost groundwater in different parts of the forests and from soil water showed values from δ13C = -13 ‰ to -27 ‰, corresponding to the ratio in

  14. Investigation of sources of atmospheric aerosol at a hot spot area in Dhaka, Bangladesh.

    Science.gov (United States)

    Begum, Bilkis A; Biswas, Swapan K; Kim, Eugene; Hopke, Philip K; Khaliquzzaman, Mohammed

    2005-02-01

    Samples of fine and coarse fractions of airborne particulate matter were collected at the Farm Gate area in Dhaka from July 2001 to March 2002. Dhaka is a hot spot area with very high pollutant concentrations because of the proximity of major roadways. The samples were collected using a "Gent" stacked filter unit in two fractions of 0- to 2.2-microm and 2.2- to 10-microm sizes. The samples were analyzed for elemental concentrations by particle-induced X-ray excitation (PIXE) and for black carbon by reflectivity methods, respectively. The data were analyzed by positive matrix factorization (PMF) to identify the possible sources of atmospheric aerosols in this area. Six sources were found for both the coarse and fine PM fractions. The data sets were also analyzed by an expanded model to explore additional sources. Seven and six factors were obtained for coarse and fine PM fractions, respectively, in these analyses. The identified sources are motor vehicle, soil dust, emissions from construction activities, sea salt, biomass burning/brick kiln, resuspended/fugitive Pb, and two-stroke engines. From the expanded modeling, approximately 50% of the total PM2.2 mass can be attributed to motor vehicles, including two-stroke engine vehicle in this hot spot in Dhaka, whereas the PMF modeling indicates that 45% of the total PM2.2 mass is from motor vehicles. The PMF2 and expanded models could resolve approximately 4% and 3% of the total PM2.2 mass as resuspended/fugitive Pb, respectively. Although, Pb has been eliminated from gasoline in Bangladesh since July 1999, there still may be substantial amounts of accumulated lead in the dust near roadways as well as fugitive Pb emissions from battery reclaimation and other industries. Soil dust is the largest component of the coarse particle fraction (PM2.2-10) accounting for approximately 71% of the total PM2.2-10 mass in the expanded model, whereas from the PMF modeling, the dust (undifferentiated) contribution is approximately 49%.

  15. Prediction of hot spot residues at protein-protein interfaces by combining machine learning and energy-based methods

    Directory of Open Access Journals (Sweden)

    Pontil Massimiliano

    2009-10-01

    Full Text Available Abstract Background Alanine scanning mutagenesis is a powerful experimental methodology for investigating the structural and energetic characteristics of protein complexes. Individual amino-acids are systematically mutated to alanine and changes in free energy of binding (ΔΔG measured. Several experiments have shown that protein-protein interactions are critically dependent on just a few residues ("hot spots" at the interface. Hot spots make a dominant contribution to the free energy of binding and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there is a need for accurate and reliable computational methods. Such methods would also add to our understanding of the determinants of affinity and specificity in protein-protein recognition. Results We present a novel computational strategy to identify hot spot residues, given the structure of a complex. We consider the basic energetic terms that contribute to hot spot interactions, i.e. van der Waals potentials, solvation energy, hydrogen bonds and Coulomb electrostatics. We treat them as input features and use machine learning algorithms such as Support Vector Machines and Gaussian Processes to optimally combine and integrate them, based on a set of training examples of alanine mutations. We show that our approach is effective in predicting hot spots and it compares favourably to other available methods. In particular we find the best performances using Transductive Support Vector Machines, a semi-supervised learning scheme. When hot spots are defined as those residues for which ΔΔG ≥ 2 kcal/mol, our method achieves a precision and a recall respectively of 56% and 65%. Conclusion We have developed an hybrid scheme in which energy terms are used as input features of machine learning models. This strategy combines the strengths of machine learning and energy-based methods. Although so far these two types of approaches have mainly been

  16. Optical and mechanical manipulation of plasmonic hot spots on gold nanoparticle tips; Optische und mechanische Manipulation plasmonischer Heisspunkte an Goldnanopartikelspitzen

    Energy Technology Data Exchange (ETDEWEB)

    Hrelescu, Calin-Alexander

    2011-06-15

    in the present thesis hybride systems based on alternative nanoparticle morphologies were studied in view of their optical properties in order to remove extensively the known limitations and insufficiencies of the established nanoparticle systems and shapes like rod-shaped or spherical nanoparticles. Star-shaped gold nanoparticles and their special plasmonic properties are presented. By methods of the dark-field spectroscopy, the photoelectron emission spectroscopy, and scanning electron microscopy the near- and far-field properties of single nanostars and their morphologies are correlated. So the first experimental proof of the localization of optically excited hot spots on the tips of the single nanostars could be given. By suited choice of the polarization and wavelength hot spots on several or exclusively single tips of a nanostar are selectively excited and the detected plasmon resonances assigned to single nanostar tips only due to experimental data. Furthermore field amplification factors in the range of 58-79 are for the first time quantitatively determined. The high and for molecules easily accessible hot spots on the tips of the nanostars are applied in order to demonstrate the excellent amplification of the Raman scattering on the level of single nanostars. The Raman amplification factors of 10{sup 7} for the studied nanostars without use of plasmonic coupling effects mark the nanostars as important candidates for the application in complex dynamical environments. A further possibility of the use of the hot spots localized on tips offer nanopyramides. By manipulation with a scanning force microscope a positioning of the hot spots until 1 nm above the surface and on arbitrary places on a sample substrate can be reached. Nanoresonators of two nanopyramides can be mechanically fabricated in three adsorption configurations concerning the tips of the two nanoparticles directed to each other. By the mechanical change of the configuration of the nanoresonator

  17. Molecular Dynamics Simulations of Hot Spots and Detonation on the Roadrunner Supercomputer

    Science.gov (United States)

    Mniszewski, Susan; Cawkwell, Marc; Germann, Timothy

    2011-06-01

    The temporal and spatial scales intrinsic to a real detonating explosive are extremely difficult to capture using molecular dynamics (MD) simulations. Nevertheless, MD remains very attractive since it allows for the resolution of dynamic phenomena at the atomic scale. We have studied the effects of spherical voids on the build up to detonation in three dimensions (3D) in a model explosive using the reactive empirical bond order (REBO) potential for the A-B system. This force field is attractive because it has been shown to support a detonation while being simple, analytic, and short-ranged. The transition from 2D to 3D simulations was facilitated by our port of the REBO force field in the parallel MD code SPaSM to LANL's petaflop Roadrunner supercomputer based on previous work by Swaminarayan and Germann [T. C. Germann et al. Concurrency Computat.: Pract. Exper. 21, 2143 (2009)]. We will provide a detailed discussion of the challenges associated with computing interatomic forces on a hybrid Opteron/Cell BE computational architecture. We will compare and contrast our results in 3D from Roadrunner with earlier 2D simulations of hot-spot assisted detonations by Heim, Herring, and co-workers [S. D. Herring et al. Phys. Rev. B, 82, 214108 (2010)].

  18. Using Activated Transport in Parallel Nanowires for Energy Harvesting and Hot-Spot Cooling

    Science.gov (United States)

    Bosisio, Riccardo; Gorini, Cosimo; Fleury, Geneviève; Pichard, Jean-Louis

    2015-05-01

    We study arrays of parallel doped semiconductor nanowires in a temperature range where the electrons propagate through the nanowires by phonon-assisted hops between localized states. By solving the random-resistor-network problem, we compute the thermopower S , the electrical conductance G , and the electronic thermal conductance Ke of the device. We investigate how those quantities depend on the position—which can be tuned with a back gate—of the nanowire impurity band with respect to the equilibrium electrochemical potential. We show that large power factors can be reached near the band edges, when S self-averages to large values while G is small but scales with the number of wires. Calculating the amount of heat exchanged locally between the electrons inside the nanowires and the phonons of the environment, we show that phonons are mainly absorbed near one electrode and emitted near the other when a charge current is driven through the nanowires near their band edges. This phenomenon could be exploited for a field control of the heat exchange between the phonons and the electrons at submicron scales in electronic circuits. It could be also used for cooling hot spots.

  19. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces

    Science.gov (United States)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D. G.; Cordeiro, Maria Natália D. S.; Gümüş, Zeynep H.; Costa, Joaquim; Bonvin, Alexandre M. J. J.; Moreira, Irina S.

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set. PMID:27472327

  20. Hot spot detection and spatio-temporal dynamics of dengue in Queensland, Australia

    Science.gov (United States)

    Naish, S.; Tong, S.

    2014-11-01

    Dengue has been a major public health concern in Australia since it re-emerged in Queensland in 1992-1993. This study explored spatio-temporal distribution and clustering of locally-acquired dengue cases in Queensland State, Australia and identified target areas for effective interventions. A computerised locally-acquired dengue case dataset was collected from Queensland Health for Queensland from 1993 to 2012. Descriptive spatial and temporal analyses were conducted using geographic information system tools and geostatistical techniques. Dengue hot spots were detected using SatScan method. Descriptive spatial analysis showed that a total of 2,398 locally-acquired dengue cases were recorded in central and northern regions of tropical Queensland. A seasonal pattern was observed with most of the cases occurring in autumn. Spatial and temporal variation of dengue cases was observed in the geographic areas affected by dengue over time. Tropical areas are potential high-risk areas for mosquito-borne diseases such as dengue. This study demonstrated that the locally-acquired dengue cases have exhibited a spatial and temporal variation over the past twenty years in tropical Queensland, Australia. There is a clear evidence for the existence of statistically significant clusters of dengue and these clusters varied over time. These findings enabled us to detect and target dengue clusters suggesting that the use of geospatial information can assist the health authority in planning dengue control activities and it would allow for better design and implementation of dengue management programs.

  1. Suppressing local hot spots due to eddy currents in magnetic coil systems

    Science.gov (United States)

    Yao, Zhen; Shojinaga, Aaron; Wu, Yong; Shvartsman, Shmaryu; Eagan, Timothy; Chmielewski, Thomas; Brown, Robert

    2011-03-01

    A particular goal in magnetic field applications is to avoid eddy current heating in coils and shields. It is important, in MRI, for example, to avoid hot spots near the patient to be imaged as well as in the vicinity of soldering joints. We develop effective analytical formulas for the eddy current behavior of sources close to surrounding conductors, we verify these via numerical simulations, and we make successful comparisons to corresponding experimental temperature distributions. Optimized patterns of incisions made in the conductors are discovered for addressing particularly troublesome heating locations. The criteria include the need to minimize the number and length of the cuts. Theory and experiment are in agreement on the efficacy of this method for reducing steady-state temperatures. An example of results in the practical design of commercial coils and shields is that a single cut parallel to the long edge of rectangular conductors reduces the temperatures much more than making multiple cuts parallel to the short edge. Supported by Ohio Third Frontier Program

  2. Evaluation of the thermal safety margin for the KMRR using the hot-spot-factor approach

    International Nuclear Information System (INIS)

    In the thermal-hydraulic (T/H) design of a reactor, several design bases are usually established at the outset and they serve throughout the design process as a set of fundamental criteria on which the adequacy of the thermal-hydraulic design can be judged. Some examples of these are the maximum fuel temperature design bases (DB), departure from nucleate boiling (DNB) BD, and maximum linear heat generation rate DB for pressurized water reactors. The same line of design approach was adopted to design the Korean Multipurpose Research Reactor to be built in the Korean Advanced Energy Research Institute by the end of 1990. The most stringent design basis for T/H design is found to be the onset of nucleate boiling (ONB) margin which is defined as the difference between the ONB wall temperature and the actual wall temperature at the hottest spot in the core. The main objective of this study is to identify what kinds of uncertainties are to be included in the core thermal-margin calculation, to set up a core thermal-margin calculation procedure into which these uncertainty effects are implemented, and to model and quantify their effects on the safety margin. The hot channel factor method for three-dimensional core thermal analysis proposed by Chelemer was used with COBRA-IV-I as the mathematical tool to evaluate the core thermal margin and its sensitivity on these uncertainties

  3. WLAN Hot Spot services for the automotive and oil industries. A business analysis

    International Nuclear Information System (INIS)

    While you refuel for gas, why not refuel for information or download vehicle data? This paper analyzes in extensive detail the user segmentation by vehicle usage, service offering, and full business models from WLAN (Wireless Local Area Network) hot spot services delivered to vehicles (private, professional, public) around gas stations. Also analyzed are the parties which play a role in such service authorization, provisioning and delivery, with all the dependencies modelled by attributed digraphs. Service planning is included as to WLAN base station capabilities. Five year financial models (CAPEX,OPEX), and data pertain to two possible service suppliers: multi-service oil companies, and mobile service operators (or MVNO). Model optimization on the return-on-investment (ROI) is carried out for different deployment scenarios, geographical coverage assumptions, as well as tariff structures. Comparison is also being made with public GPRS data services, as precursors for 3G services, and the effect of WLAN roaming is analyzed. Analysis shows that due to manpower costs and marketing costs, suitable ROI will not be achieved unless externalities are accounted for and innovative tariff structures are introduced. Open issues and further research are outlined. Further work is carried out, also with automotive electronics sector, wireless systems providers, wireless terminals platform suppliers, and vehicle manufacturers

  4. Direct simulations of homogeneous bubble nucleation: Agreement with classical nucleation theory and no local hot spots.

    Science.gov (United States)

    Diemand, Jürg; Angélil, Raymond; Tanaka, Kyoko K; Tanaka, Hidekazu

    2014-11-01

    We present results from direct, large-scale molecular dynamics simulations of homogeneous bubble (liquid-to-vapor) nucleation. The simulations contain half a billion Lennard-Jones atoms and cover up to 56 million time steps. The unprecedented size of the simulated volumes allows us to resolve the nucleation and growth of many bubbles per run in simple direct micro-canonical simulations while the ambient pressure and temperature remain almost perfectly constant. We find bubble nucleation rates which are lower than in most of the previous, smaller simulations. It is widely believed that classical nucleation theory (CNT) generally underestimates bubble nucleation rates by very large factors. However, our measured rates are within two orders of magnitude of CNT predictions; only at very low temperatures does CNT underestimate the nucleation rate significantly. Introducing a small, positive Tolman length leads to very good agreement at all temperatures, as found in our recent vapor-to-liquid nucleation simulations. The critical bubbles sizes derived with the nucleation theorem agree well with the CNT predictions at all temperatures. Local hot spots reported in the literature are not seen: Regions where a bubble nucleation event will occur are not above the average temperature, and no correlation of temperature fluctuations with subsequent bubble formation is seen.

  5. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces.

    Science.gov (United States)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D G; Cordeiro, Maria Natália D S; Gümüş, Zeynep H; Costa, Joaquim; Bonvin, Alexandre M J J; Moreira, Irina S

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set. PMID:27472327

  6. The Effect of Particle Properties on Hot Particle Spot Fire Ignition

    Science.gov (United States)

    Zak, Casey David

    The ignition of natural combustible material by hot metal particles is an important fire ignition pathway by which wildland and wildland-urban-interface spot fires are started. There are numerous cases reported of wild fires started by clashing power-lines or from sparks generated by machines or engines. Similarly there are many cases reported of fires caused by grinding, welding and cutting sparks. Up to this point, research on hot particle spot fire ignition has largely focused on particle generation and transport. A small number of studies have examined what occurs after a hot particle contacts a natural fuel bed, but until recently the process remained poorly understood. This work describes an investigation of the effect of particle size, temperature and thermal properties on the ability of hot particles to cause flaming ignition of cellulosic fuel beds. Both experimental and theoretical approaches are used, with a focus on understanding the physics underlying the ignition process. For the experimental study, spheres of stainless steel, aluminum, brass and copper are heated in a tube furnace and dropped onto a powdered cellulose fuel bed; the occurrence of flaming ignition or lack thereof is visually observed and recorded. This procedure is repeated a large number of times for each metal type, varying particle diameter from 2 to 11 mm and particle temperature between 575 and 1100°C. The results of these experiments are statistically analyzed to find approximate ignition boundaries and identify boundary trends with respect to the particle parameters of interest. Schlieren images recorded during the ignition experiments are also used to more accurately describe the ignition process. Based on these images, a simple theoretical model of hot particle spot fire ignition is developed and used to explore the experimental trends further. The model under-predicts the minimum ignition temperatures required for small spheres, but agrees qualitatively with the experimental

  7. Solar hot spot phenomenon and its analysis%太阳电池热斑现象和成因的分析

    Institute of Scientific and Technical Information of China (English)

    伊纪禄; 刘文祥; 马洪斌; 王晟

    2012-01-01

    The hot spot effect is very common in the application of solar cell,and the hot spot seriously affect the performance of solar cells and its service life with a great danger.So it's important to study the influence factors of the hot spot effect and reduce the risk of hot spot.The influence factors of the hot spot were analyzed according to the hot spot phenomenon.Combined with the hot spot test experiences in laboratory and the related experimental verifications,the analysis find that the hot spot and temperature have a considerable relationship,and the internal factors of hot spot mainly include the dark current and internal resistance.%热斑效应在太阳电池的实际应用中非常普遍,而且热斑效应严重影响太阳电池的性能和寿命,并有很大的危险性.研究热斑效应的影响因素,降低热斑效应危险性至关重要.根据热斑效应产生的现象,结合实验室所做的热斑试验经验,经过充足的相关试验验证,分析热斑效应的影响因素.分析发现热斑效应与温度有相当大的关系,影响热斑效应的内在因素主要有暗电流和内阻.

  8. X-ray Radiation Mechanisms and the Beaming Effect of Hot Spots and Knots in AGN Jets

    Indian Academy of Sciences (India)

    Jin Zhang; Jin-Ming Bai; Liang Chen; Enwei Liang

    2011-03-01

    The observed broadband spectral energy distributions (SEDs) of 22 hot spots and 45 knots are modelled with single-zone lepton models. Considering the sources at rest, the X-rays of some hot spots can be explained by the SSC model with magnetic field being consistent with the equipartition magnetic field in magnitude of order 1, but at the same time an unreasonably low magnetic field is required to model the X-rays for all knots. When considering the relativistic bulk motion of the sources, the IC/CMB model well explains the X-ray emission for most of them under the equipartition condition. We show that the ratio of observational luminosity is tentatively correlated with the co-moving equipartition magnetic field 'eq and the beaming factor . These facts suggest that the observational differences of the X-rays from the knots and hot spots may be mainly due to the differences in the Doppler boosting effect and the co-moving magnetic field of the two kinds of source.

  9. Controlling dynamic SERS hot spots on a monolayer film of Fe3O4@Au nanoparticles by a magnetic field

    Science.gov (United States)

    Guo, Qing-Hua; Zhang, Chen-Jie; Wei, Chao; Xu, Min-Min; Yuan, Ya-Xian; Gu, Ren-Ao; Yao, Jian-Lin

    2016-01-01

    A large surface-enhanced Raman scattering (SERS) effect is critically dependent on the gap distance of adjacent nanostructures, i.e., "hot spots". However, the fabrication of dynamically controllable hot spots still remains a remarkable challenge. In the present study, we employed an external magnetic field to dynamically control the interparticle spacing of a two-dimensional monolayer film of Fe3O4@Au nanoparticles at a hexane/water interface. SERS measurements were performed to monitor the expansion and shrinkage of the nanoparticles gaps, which produced an obvious effect on SERS activities. The balance between the electrostatic repulsive force, surface tension, and magnetic attractive force allowed observation of the magnetic-field-responsive SERS effect. Upon introduction of an external magnetic field, a very weak SERS signal appeared initially, indicating weak enhancement due to a monolayer film with large interparticle spacing. The SERS intensity reached maximum after 5 s and thereafter remained almost unchanged. The results indicated that the observed variations in SERS intensities were fully reversible after removal of the external magnetic field. The reduction of interparticle spacing in response to a magnetic field resulted in about one order of magnitude of SERS enhancement. The combined use of the monolayer film and external magnetic field could be developed as a strategy to construct hot spots both for practical application of SERS and theoretical simulation of enhancement mechanisms.

  10. WiFi Hot Spot Service Business for the Automotive and Oil Industries: A Competitive Analysis

    Directory of Open Access Journals (Sweden)

    Louis-Francois PAU

    2010-01-01

    Full Text Available While you refuel for gas, why not refuel for information or upload vehicle data, using a cheap wireless technology as WiFi? This paper analyzes in extensive detail the user segmentation by vehicle usage, service offering, and full business models from WiFi hot spot services delivered to and from vehicles (private, professional, public around gas stations. Are also analyzed the parties which play a role in such services: authorization, provisioning and delivery, with all the dependencies modelled by attributed digraphs. Account is made of WiFi base station technical capabilities and costs. Five year financial models (CAPEX, OPEX, and data pertain to two possible service suppliers: multi-service oil companies, and mobile service operators (or MVNOs. Model optimization on the return-on-investment (R.O.I. is carried out for different deployment scenarios, geographical coverage assumptions, as well as tariff structures. Comparison is also being made with public GPRS and 3G data services, as precursors to HSPA/LTE, and the effect of WiFi roaming is analyzed. Regulatory implications, including those dealing with public safety, are addressed. Analysis shows that due to manpower costs and marketing costs, suitable R.O.I. will not be achieved unless externalities are accounted for and innovative tariff structures are introduced. Open issues and further research are outlined. Further work is currently carried out with automotive electronics sector, wireless systems providers, wireless terminals platform suppliers, and vehicle manufacturers. Future relevance of this work is also discussed for the emerging electrical reloading grids for electrical vehicles.

  11. Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II.

    Science.gov (United States)

    Kim, Jung-Wook; Hu, Jan C-C; Lee, Jae-Il; Moon, Sung-Kwon; Kim, Young-Jae; Jang, Ki-Taeg; Lee, Sang-Hoon; Kim, Chong-Chul; Hahn, Se-Hyun; Simmer, James P

    2005-02-01

    The current system for the classification of hereditary defects of tooth dentin is based upon clinical and radiographic findings and consists of two types of dentin dysplasia (DD) and three types of dentinogenesis imperfecta (DGI). However, whether DGI type III should be considered a distinct phenotype or a variation of DGI type II is debatable. In the 30 years since the classification system was first proposed, significant advances have been made regarding the genetic etiologies of inherited dentin defects. DGI type II is recognized as an autosomal dominant disorder with almost complete penetrance and a low frequency of de novo mutations. We have identified a mutation (c.52G-->T, p.V18F) at the first nucleotide of exon 3 of the DSPP (dentin sialophosphoprotein) gene in a Korean family (de novo) and a Caucasian family. This mutation has previously been reported as causing DGI type II in a Chinese family. These findings suggest that this mutation site represents a mutational "hot spot" in the DSPP gene. The clinical and radiographic features of these two families include the classic phenotypes associated with both DGI type II and type III. Finding that a single mutation causes both phenotypic patterns strongly supports the conclusion that DGI type II and DGI type III are not separate diseases but rather the phenotypic variation of a single disease. We propose a modification of the current classification system such that the designation "hereditary opalescent dentin" or "DGI type II" should be used to describe both the DGI type II and type III phenotypes.

  12. Hot Spots of Mercury Bioaccumulation in Amphibian Populations From the Conterminous United States

    Science.gov (United States)

    Bank, M. S.

    2008-12-01

    Mercury (Hg) contamination in the United States (U.S.) is well-documented and continues to be a public- health issue of great concern. Fish consumption advisories have been issued throughout much of the U.S. due to elevated levels of methylmercury (MeHg). Methylmercury contamination in the developing fetus and in young children is a major public health issue for certain sectors of the global human population. Moreover, identifying MeHg hot spots and the effects of MeHg pollution on environmental health and biodiversity are also considered a high priority for land managers, risk assessors, and conservation scientists. Despite their overall biomass and importance to aquatic and terrestrial ecosystems, Hg and MeHg bioaccumulation dynamics and toxicity in amphibians are not well studied, especially when compared to other vertebrate taxa such as birds, mammals, and fish species. Population declines in amphibians are well documented and likely caused by synergistic and interacting, multiple stressors such as climate change, exposure to toxic pollutants, fungal pathogens, and habitat loss and ecosystem degradation. Protecting quality of terrestrial ecosystems in the U.S. has enormous ramifications for economic and public health of the nation's residents and is fundamental to maintaining the biotic integrity of surface waters, riparian zones, and environmental health of forested landscapes nationwide. Determining Hg concentration levels for terrestrial and surface water ecosystems also has important implications for protecting the nation's fauna. Here I present an overview of the National Amphibian Mercury Program and evaluate variation in MeHg hotspots, Hg bioaccumulation and distribution in freshwater and terrestrial habitats across a broad gradient of physical, climatic, biotic, and ecosystem settings to identify the environmental conditions and ecosystem types that are most sensitive to Hg pollution. The role of geography, disturbance mechanisms, and abiotic and biotic

  13. Cooling water of power plant creates "hot spots" for tropical fishes and parasites.

    Science.gov (United States)

    Emde, Sebastian; Kochmann, Judith; Kuhn, Thomas; Dörge, Dorian D; Plath, Martin; Miesen, Friedrich W; Klimpel, Sven

    2016-01-01

    Thermally altered water bodies can function as "hot spots" where non-native species are establishing self-sustaining populations beyond their tropical and subtropical native regions. Whereas many tropical fish species have been found in these habitats, the introduction of non-native parasites often remains undetected. Here, n = 77 convict cichlids (Amatitlania nigrofasciata) were sampled by electro-fishing at two sites from a thermally altered stream in Germany and examined for parasite fauna and feeding ecology. Stomach content analysis suggests an opportunistic feeding strategy of A. nigrofasciata: while plant material dominated the diet at the warm water inlet (∼30 °C), relative contributions of insects, plants, and crustaceans were balanced 3 km downstream (∼27 °C). The most abundant non-native parasite species was the tropical nematode Camallanus cotti with P = 11.90 % and P = 80.00 % at the inlet and further downstream, respectively. Additionally, nematode larvae of Anguillicoloides crassus and one specimen of the subtropical species Bothriocephalus acheilognathi were isolated. A. nigrofasciata was also highly infected with the native parasite Acanthocephalus anguillae, which could be linked to high numbers of the parasite's intermediate host Asellus aquaticus. The aim of this study was to highlight the risk and consequences of the release and establishment of ornamental fish species for the introduction and spread of non-indigenous metazoan parasites using the convict cichlid as a model species. Furthermore, the spread of non-native parasites into adjacent fish communities needs to be addressed in the future as first evidence of Camallanus cotti in native fish species was also found. PMID:26374537

  14. Thermal screening of facial skin arterial hot spots using non-contact infrared radiometry

    International Nuclear Information System (INIS)

    Non-contact infrared thermometry of facial skin offers advantages over less accessible internal body sites, especially when considering mass screening for febrile infectious disease. The forehead offers an obvious site, but does not present an isothermic surface, as various small arteries passing close to the surface create 'hot-spots'. The aim of this study is to use non-contact infrared (IR) thermometry to determine the link between the temperature at specific facial skin sites and clinical body temperature. A sample of 169 asymptomatic adults (age range 18–54 years) was screened with IR thermometers (Braun Thermoscan proLT for auditory meatus (AM) temperature representing clinical body temperature, and a Raytek, Raynger MX for skin surface temperature). Peak IR skin temperature was measured over the course of each posterior auricular artery (PAA) and each superficial temporal artery (STA). In a sub-group (n = 54) the peak skin temperature of the forehead's metopic region (MR) was also recorded. There were no differences (P > 0.05) between the PAA and STA at 34.2 ± 0.9 °C and 34.2 ± 0.7 °C, respectively, which were 2.5 °C cooler than the AM temperature (36.7 ± 0.5 °C, p 2 = 0.63, p < 0.001) between PAA and STA. There were no asymmetric temperature differences between the left and right sides and males had warmer skin over the MR (F, 33.6 ± 0.7 °C versus M, 34.4 ± 0.6 °C, p < 0.001). Although a lack of correlation between either PAA or STA and AM was apparent in asymptomatics, further research in symptomatics is required to determine the usefulness of these measurements in mass screening of conditions such as fever

  15. Shock Compression Induced Hot Spots in Energetic Material Detected by Thermal Imaging Microscopy

    Science.gov (United States)

    Chen, Ming-Wei; Dlott, Dana

    2014-06-01

    The chemical reaction of powder energetic material is of great interest in energy and pyrotechnic applications since the high reaction temperature. Under the shock compression, the chemical reaction appears in the sub-microsecond to microsecond time scale, and releases a large amount of energy. Experimental and theoretical research progresses have been made in the past decade, in order to characterize the process under the shock compression. However, the knowledge of energy release and temperature change of this procedure is still limited, due to the difficulties of detecting technologies. We have constructed a thermal imaging microscopy apparatus, and studied the temperature change in energetic materials under the long-wavelength infrared (LWIR) and ultrasound exposure. Additionally, the real-time detection of the localized heating and energy concentration in composite material is capable with our thermal imaging microscopy apparatus. Recently, this apparatus is combined with our laser driven flyer plate system to provide a lab-scale source of shock compression to energetic material. A fast temperature increase of thermite particulars induced by the shock compression is directly observed by thermal imaging with 15-20 μm spatial resolution. Temperature change during the shock loading is evaluated to be at the order of 10^9K/s, through the direct measurement of mid-wavelength infrared (MWIR) emission intensity change. We observe preliminary results to confirm the hot spots appear with shock compression on energetic crystals, and will discuss the data and analysis in further detail. M.-W. Chen, S. You, K. S. Suslick, and D. D. Dlott, {Rev. Sci. Instr., 85, 023705 (2014) M.-W. Chen, S. You, K. S. Suslick, and D. D. Dlott, {Appl. Phys. Lett., 104, 061907 (2014)} K. E. Brown, W. L. Shaw, X. Zheng, and D. D. Dlott, {Rev. Sci. Instr., 83, 103901 (2012)}

  16. Cooling water of power plant creates "hot spots" for tropical fishes and parasites.

    Science.gov (United States)

    Emde, Sebastian; Kochmann, Judith; Kuhn, Thomas; Dörge, Dorian D; Plath, Martin; Miesen, Friedrich W; Klimpel, Sven

    2016-01-01

    Thermally altered water bodies can function as "hot spots" where non-native species are establishing self-sustaining populations beyond their tropical and subtropical native regions. Whereas many tropical fish species have been found in these habitats, the introduction of non-native parasites often remains undetected. Here, n = 77 convict cichlids (Amatitlania nigrofasciata) were sampled by electro-fishing at two sites from a thermally altered stream in Germany and examined for parasite fauna and feeding ecology. Stomach content analysis suggests an opportunistic feeding strategy of A. nigrofasciata: while plant material dominated the diet at the warm water inlet (∼30 °C), relative contributions of insects, plants, and crustaceans were balanced 3 km downstream (∼27 °C). The most abundant non-native parasite species was the tropical nematode Camallanus cotti with P = 11.90 % and P = 80.00 % at the inlet and further downstream, respectively. Additionally, nematode larvae of Anguillicoloides crassus and one specimen of the subtropical species Bothriocephalus acheilognathi were isolated. A. nigrofasciata was also highly infected with the native parasite Acanthocephalus anguillae, which could be linked to high numbers of the parasite's intermediate host Asellus aquaticus. The aim of this study was to highlight the risk and consequences of the release and establishment of ornamental fish species for the introduction and spread of non-indigenous metazoan parasites using the convict cichlid as a model species. Furthermore, the spread of non-native parasites into adjacent fish communities needs to be addressed in the future as first evidence of Camallanus cotti in native fish species was also found.

  17. A study of the long-term properties of Jovian hot spots from HST and ground-based observations between 1994 and 1998

    Science.gov (United States)

    Arregui, E.; Rojas, J. F.; Sanchez-Lavega, A.; Lecacheux, J.; Colas, F.; Miyazaki, I.; Parker, D.

    2000-10-01

    We have used the HST-WFPC2 archived images of Jupiter in the period 1994-1998 together with a large set of CCD ground based images, to study the zonal distribution, long-term motions, lifetimes, interactions and other properties of the hot spot - plume regions at 7 degrees North. Red and near infrared filters covering the wavelength range 650 - 953 nm have been used since they show the hot spots with a high contrast. We have found that the hot spots have velocities ranging from 95 to 112 m/s and are grouped typically in families of three to six members. We do not found any correlation between their velocity and wavenumber. The long-term survey allowed us to identify mergers and splitting of the hot spots areas. The Spanish team was supported by Gobierno Vasco PI 034/97. The French team was supported by the "Programme National de Planetologie."

  18. Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

    CERN Document Server

    Dietrich, Wieland; Hori, Kumiko

    2015-01-01

    Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typ...

  19. A Radio through X-ray Study of the Hot Spots, Active Nucleus, and Environment of the Nearby FR II Radio Galaxy 3C 33

    CERN Document Server

    Kraft, R P; Hardcastle, M J; Evans, D A; Croston, J H; Worrall, D M; Murray, S S

    2007-01-01

    We present results from {\\em Chandra}/ACIS-S, {\\em Spitzer}, {\\em XMM-Newton}, {\\em HST}, and VLA observations of the radio hot spots, extended environment, and nucleus of the nearby ($z$=0.0597) FR II radio galaxy 3C 33. This is a relatively low-power FR II radio galaxy, and so we expect, {\\it a priori}, to detect a significant X-ray synchrotron component to the emission from the hot spots. We detect X-ray emission coincident with the two knots of polarized optical emission from the southern hot spot (SHS), as well as along the northwest arm of this hot spot. We also detect X-ray emission from two compact regions of the northern hot spot (NHS), as well as diffuse emission behind the radio peak. The X-ray flux density of the region at the tip of the southern hot spot, the most compact radio feature of the southern lobe, is consistent with the synchrotron self-Compton (SSC) process. The X-ray flux densities of the other three regions of the SHS and the two compact regions of the NHS are an order of magnitude o...

  20. The topographic wetness index as a predictor for hot spots of DOC export from catchments

    Science.gov (United States)

    Musolff, Andreas; Oosterwoud, Marieke; Tittel, Jörg; Selle, Benny; Fleckenstein, Jan H.

    2015-04-01

    Dissolved organic carbon (DOC) concentrations in the discharge of many catchments in Europe and North America are rising. This increase is of concern for the drinking water supply from reservoirs since high DOC concentrations cause additional costs in water treatment and potentially the formation of harmful disinfection by-products. A prerequisite for understanding this increase is the knowledge on the spatial distribution of dominant soil DOC sources within catchments and on mobilization as well as transfer processes to the surface water. A number of studies identified wetland soils as the dominant source with fast mobilization and short transit times to the receiving surface water. However, most studies have either focussed on smaller, hillslope and single catchment or on larger scale multi-catchment assessments. Moreover, information on the distribution of soil types in catchments is not always readily available. This study brings together both types of assessment in a data-driven top-down approach: (i) a detailed survey on DOC concentration and loads over the course of one year within two paired data-rich catchments discharging into a large drinking water reservoir in central Germany and (ii) a database of hydrochemistry and physio-geographic characteristics of 113 catchments draining into 58 reservoirs across Germany over the course of 16 years. The objective is to define hot spots of DOC export within the catchments for both types of assessments (i, ii) and to test the suitability of the topographic wetness index (TWI) as a proxy for well-connected wetland soils at various spatial scales. In the sub-catchments of assessment (i) the spatial variability of concentrations and loads was much smaller than expected. None of the studied sub-catchments was a predominant producer of the total DOC loads exported from the catchments. We found the mean concentrations and loads to be positively correlated with the share of groundwater-dominated soils in the sub

  1. Spatial Nutrient Variability in a Sierran Forest Soil: an Investigation into the Nature and Potential Causes of Nutrient Hot Spots

    Science.gov (United States)

    Johnson, D. W.; Miller, W. W.; Rau, B. M.; Meadows, M. W.

    2010-12-01

    Because of the extremely dry summers, rooting is entirely absent in the O horizons of many forest ecosystems in the eastern Sierra Nevada Mountains of Nevada and California. Thus, decomposition/N mineralization and vegetation uptake processes are spatially discoupled, and the intense competition for N between roots and decomposers in the O horizon which characterizes more humid forest ecosystems is absent. Because of this discoupling, the N returned in littterfall is not recycled to the trees until: 1) N supply exceeds microbial demand, and 2) N is leached to lower horizons where roots are present. Both O horizons and the mineral soil surface in these ecosystems are extremely hydrophobic in summer, restricting the ability of summer rainfall to wet underlying mineral soils except via preferential flowpaths. Recent studies have found very high concentrations of ionic forms of N in O horizon interflow solutions that flow over the top of mineral soils. We hypothesize that this O horizon interflow creates biogeochemical “hot spots” where it infiltrates into preferential flowpaths present in the mineral soil (Bundt et al., 2001). This paper reports the results of a study aimed at detecting O horizon runoff and nutrient hot spots in soils of the King’s River Experimental Watershed (KREW) in the western Sierra Nevada Mountains of California, one of the Critical Zone Observatory sites. Over two winter seasons, we found substantial amounts of O horizon interflow, some of which was highly enriched in inorganic forms of N and P. Measurements of nutrient variability by resin based collectors and coring within in small plots (6 x 6 m) revealed the presence of hot spots (defined as statistical outliers) and a varying degrees of positive skew for all measured nutrients, with the degree of skew and prevalence of hotspots being greater with weaker extractants. For example, skew was greatest and the hotspots were most prevalent for water soluble ammonium and nitrate, less for

  2. Hot Spots and Mantle Plumes: A Window Into the Deep Earth and a Lesson on How Science Really Works

    Science.gov (United States)

    Caplan-Auerbach, J.

    2010-12-01

    Despite years of discussion, debate and controversy over the causes of ocean island volcanism, most students simply learn that such features form from fixed plumes of hot material rising from the core mantle boundary. Although we know that the Hawaiian plume exhibited substantial southward motion, most introductory geology textbooks still report that hot spots are fixed and that the Hawaiian-Emperor bend reflects a change in plate motion. That mantle plumes are the focus of significant controversy within the scientific community is rarely, if ever, discussed, and alternative models for the formation of intraplate volcanoes are ignored. Students may thus complete their studies without learning about the dynamic debate focused on the existence and formation of mantle plumes. This issue represents an opportunity for students to see how science really works, how new models are constructed, and what distinguishes a hypothesis from a theory. The culminating project in Western Washington University’s Introduction to Geophysics class, a course required for the BS degree in geology, focuses on the hot spot and mantle plume debate. For the first nine weeks of the quarter students learn about general topics in geophysics including plate tectonics, magnetism, seismology, gravity and heat flow. At the end of the course, students break into small research groups with the goal of investigating how geophysics may be used to address three questions: (1) Do ocean island volcanoes form from mantle plumes? (2) Are “hot spots” actually hot? (3) Are hot spots stationary? Each group examines how these questions may be addressed using a specific geophysical tool. In addition to the five topics described above, a sixth group investigates the question of “if not hot spots/mantle plumes, how do ocean island volcanoes form?” Students read the current literature on the topic and present their results to their classmates. Presentations focus on topics such as the use of seismic

  3. Bering-Okhotsk Seal Survey (BOSS) Identified Hot Spots (2012-13)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — US surveys were conducted of the Bering Sea pack ice for bearded, spotted, ribbon, and ringed seals using digital cameras and thermal imagers mounted in the belly...

  4. The southern stratospheric gravity-wave hot spot: individual waves and their momentum fluxes measured by COSMIC GPS-RO

    Directory of Open Access Journals (Sweden)

    N. P. Hindley

    2015-02-01

    Full Text Available During austral winter the mountains of the southern Andes and Antarctic Peninsula are a known hot spot of intense gravity wave momentum flux. There also exists a long leeward region of increased gravity wave energy that sweeps eastwards from the mountains out over the Southern Ocean, the source of which has historically proved difficult to determine. In this study we use Global Positioning System (GPS Radio Occultation (RO data from the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC satellite constellation to investigate the distribution, variability and sources of waves in the hot spot region and over the Southern Ocean. We present evidence that suggests a southward focusing of waves into the stratospheric jet from sources to the north. We also describe a wavelet analysis technique for the quantitative identification of individual waves from COSMIC temperature profiles. This analysis reveals different geographical regimes of wave amplitude and short-timescale variability in the wave field over the Southern Ocean. Finally, we take advantage of the large numbers of closely spaced pairs of profiles from the deployment phase of the COSMIC constellation in 2006 to make estimates of gravity wave horizontal wavelengths. We show that, given sufficient numbers of these pairs, GPS-RO can then produce physically reasonable estimates of stratospheric gravity wave momentum flux in the hot spot region that are consistent with other studies. The results are discussed in the context of previous satellite and modelling studies to build up a better picture of the nature and origins of waves in the southern winter stratosphere.

  5. Finite volume analysis of temperature effects induced by active MRI implants: 2. Defects on active MRI implants causing hot spots

    Directory of Open Access Journals (Sweden)

    Grönemeyer Dietrich HW

    2006-05-01

    Full Text Available Abstract Background Active magnetic resonance imaging implants, for example stents, stent grafts or vena cava filters, are constructed as wireless inductively coupled transmit and receive coils. They are built as a resonator tuned to the Larmor frequency of a magnetic resonance system. The resonator can be added to or incorporated within the implant. This technology can counteract the shielding caused by eddy currents inside the metallic implant structure. This may allow getting diagnostic information of the implant lumen (in stent stenosis or thrombosis for example. The electro magnetic rf-pulses during magnetic resonance imaging induce a current in the circuit path of the resonator. A by material fatigue provoked partial rupture of the circuit path or a broken wire with touching surfaces can set up a relatively high resistance on a very short distance, which may behave as a point-like power source, a hot spot, inside the body part the resonator is implanted to. This local power loss inside a small volume can reach ¼ of the total power loss of the intact resonating circuit, which itself is proportional to the product of the resonator volume and the quality factor and depends as well from the orientation of the resonator with respect to the main magnetic field and the imaging sequence the resonator is exposed to. Methods First an analytical solution of a hot spot for thermal equilibrium is described. This analytical solution with a definite hot spot power loss represents the worst case scenario for thermal equilibrium inside a homogeneous medium without cooling effects. Starting with this worst case assumptions additional conditions are considered in a numerical simulation, which are more realistic and may make the results less critical. The analytical solution as well as the numerical simulations use the experimental experience of the maximum hot spot power loss of implanted resonators with a definite volume during magnetic resonance imaging

  6. Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Maza, S.; Valencia, R.; Geworski, L.; Zander, A.; Munz, D.L. [Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Schumannstrasse 20-21, 10117 Berlin (Germany); Draeger, E.; Winter, H.; Sterry, W. [Clinic for Dermatology, Venereology and Allergology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany)

    2002-10-01

    Detection of the ''true'' sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the

  7. Environmental hot spot analysis in agricultural life-cycle assessments – three case studies

    Directory of Open Access Journals (Sweden)

    Gerhard Piringer

    2016-06-01

    Full Text Available Present-day agricultural technology is facing the challenge of limiting the environmental impacts of agricultural production – such as greenhouse gas emissions and demand for additional land – while meeting growing demands for agricultural products. Using the well-established method of life-cycle assessment (LCA, potential environmental impacts of agricultural production chains can be quantified and analyzed. This study presents three case studies of how the method can pinpoint environmental hot spots at different levels of agricultural production systems. The first case study centers on the tractor as the key source of transportation and traction in modern agriculture. A common Austrian tractor model was investigated over its life-cycle, using primary data from a manufacturer and measured load profiles for field work. In all but one of the impact categories studied, potential impacts were dominated by the operation phase of the tractor’s life-cycle (mainly due to diesel fuel consumption, with 84.4-99.6% of total impacts. The production phase (raw materials and final assembly caused between 0.4% and 12.1% of impacts, while disposal of the tractor was below 1.9% in all impact categories. The second case study shifts the focus to an entire production chain for a common biogas feedstock, maize silage. System boundaries incorporate the effect of auxiliary materials such as fertilizer and pesticides manufacturing and application. The operation of machinery in the silage production chain was found to be critical to its environmental impact. For the climate change indicator GWP100 (global warming potential, 100-year reference period, emissions from tractor operation accounted for 15 g CO2-eq per kg silage (64% of total GWP100, followed by field emissions during fertilizer (biogas digestate application with 6 g CO2-eq per kg silage (24% of total GWP100. At a larger system scale that includes a silage-fed biogas plant with electricity generated by

  8. Resolving hot spots in the C-terminal dimerization domain that determine the stability of the molecular chaperone Hsp90.

    Directory of Open Access Journals (Sweden)

    Emanuele Ciglia

    Full Text Available Human heat shock protein of 90 kDa (hHsp90 is a homodimer that has an essential role in facilitating malignant transformation at the molecular level. Inhibiting hHsp90 function is a validated approach for treating different types of tumors. Inhibiting the dimerization of hHsp90 via its C-terminal domain (CTD should provide a novel way to therapeutically interfere with hHsp90 function. Here, we predicted hot spot residues that cluster in the CTD dimerization interface by a structural decomposition of the effective energy of binding computed by the MM-GBSA approach and confirmed these predictions using in silico alanine scanning with DrugScore(PPI. Mutation of these residues to alanine caused a significant decrease in the melting temperature according to differential scanning fluorimetry experiments, indicating a reduced stability of the mutant hHsp90 complexes. Size exclusion chromatography and multi-angle light scattering studies demonstrate that the reduced stability of the mutant hHsp90 correlates with a lower complex stoichiometry due to the disruption of the dimerization interface. These results suggest that the identified hot spot residues can be used as a pharmacophoric template for identifying and designing small-molecule inhibitors of hHsp90 dimerization.

  9. Hot spots and transient pockets: predicting the determinants of small-molecule binding to a protein-protein interface.

    Science.gov (United States)

    Metz, Alexander; Pfleger, Christopher; Kopitz, Hannes; Pfeiffer-Marek, Stefania; Baringhaus, Karl-Heinz; Gohlke, Holger

    2012-01-23

    Protein-protein interfaces are considered difficult targets for small-molecule protein-protein interaction modulators (PPIMs ). Here, we present for the first time a computational strategy that simultaneously considers aspects of energetics and plasticity in the context of PPIM binding to a protein interface. The strategy aims at identifying the determinants of small-molecule binding, hot spots, and transient pockets, in a protein-protein interface in order to make use of this knowledge for predicting binding modes of and ranking PPIMs with respect to their affinity. When applied to interleukin-2 (IL-2), the computationally inexpensive constrained geometric simulation method FRODA outperforms molecular dynamics simulations in sampling hydrophobic transient pockets. We introduce the PPIAnalyzer approach for identifying transient pockets on the basis of geometrical criteria only. A sequence of docking to identified transient pockets, starting structure selection based on hot spot information, RMSD clustering and intermolecular docking energies, and MM-PBSA calculations allows one to enrich IL-2 PPIMs from a set of decoys and to discriminate between subgroups of IL-2 PPIMs with low and high affinity. Our strategy will be applicable in a prospective manner where nothing else than a protein-protein complex structure is known; hence, it can well be the first step in a structure-based endeavor to identify PPIMs. PMID:22087639

  10. The Hexapeptide Repeated Segment LIAGY is a Hot Spot of Aggregation of the Pseudomonas syringae Ice Nucleation Protein.

    Science.gov (United States)

    Di Martino, Patrick

    2016-01-01

    Ice nucleation proteins (INPs) form oligomeric structures by self-assembly and aggregation. We looked for the presence of potential aggregating sequences inside the INP from Pseudomonas syringae by a computational approach with the AGGRESCAN, FOMDAMYLOID and TANGO softwares. A total of 38 hot spots of aggregation were predicted in the INP sequence: 7 localized in the Nterminal domain, 2 in the C-terminal region, 28 in the highly repetitive central (HRC) region and 1 shared between the HRC and the Carboxyl-terminus regions of the protein. All the hot spots of aggregation identified in the HRC domain overlapped a 8-residue low fidelity repeat including a LIAGYrelated sequence. We confirmed the predictions by an experimental approach using synthetic peptides corresponding to different parts of the INP central sequence, absorbance spectroscopy and fluorescence spectroscopy in the presence of Congo red (CR) or Thioflavin T (ThT), respectively. Peptide 620-SFIIAGYG-627 predicted to aggregate by the three softwares induced an increase in fluorescence of ThT. Peptide 729-GFKSILTAGY-738 predicted to aggregate by AGGRESCAN and FOLDAMYLOID induced a shift in the maximum of absorbance of CR. Peptide 1124-SVLTAGA-1130 predicted to aggregate only by TANGO did not interfere with CR absorbance or ThT fluorescence. In conclusion, the use of three aggregation prediction algorithms and two biochemical assays showed that the hexapeptide repeated segment LIAGY, previously shown to form a hairpin loop may be involved in the aggregation of the P. syringae INP. PMID:26548995

  11. Identification of Interaction Hot Spots in Structures of Drug Targets on the Basis of Three-Dimensional Activity Cliff Information.

    Science.gov (United States)

    Furtmann, Norbert; Hu, Ye; Gütschow, Michael; Bajorath, Jürgen

    2015-12-01

    Activity cliffs are defined as pairs or groups of structurally similar or analogous compounds that share the same specific activity but have large differences in potency. Although activity cliffs are mostly studied in medicinal chemistry at the level of molecular graphs, they can also be assessed by comparing compound binding modes. If such three-dimensional activity cliffs (3D-cliffs) are studied on the basis of X-ray complex structures, experimental ligand-target interaction details can be taken into account. Rapid growth in the number of 3D-cliffs that can be derived from X-ray complex structures has made it possible to identify targets for which a substantial body of 3D-cliff information is available. Activity cliffs are typically studied to identify structure-activity relationship determinants and aid in compound optimization. However, 3D-cliff information can also be used to search for interaction hot spots and key residues, as reported herein. For six of seven drug targets for which more than 20 3D-cliffs were available, series of 3D-cliffs were identified that were consistently involved in interactions with different hot spots. These 3D-cliffs often encoded chemical modifications resulting in interactions that were characteristic of highly potent compounds but absent in weakly potent ones, thus providing information for structure-based design.

  12. An Analytical Model for Torus Networks in the Presence of Batch Message Arrivals with Hot-spot Destinations

    Institute of Scientific and Technical Information of China (English)

    Yulei Wu; Geyong Min; Mohamed Ould-Khaoua; Hao Yin

    2009-01-01

    Interconnection networks are hardware fabrics supporting communications between individual processors in multicomputers.The low-dimensional k-ary n-cubes (or torus) with adaptive wormhole switching have attracted significant research efforts to construct high-performance interconnection networks in contemporary multi-computers.The arrival process and destination distribution of messages have great effects on network performance.With the aim of capturing the characteristics of the realistic traffic pattern and obtaining a deep understanding of the performance behaviour of interconnection networks,this paper presents an analytical model to investigate the message latency in adaptive-routed wormhole-switched torus networks where there exists hot-spot nodes and the message arrivals follow a batch arrival process.Each generated message has a given probability to be directed to the hot-spot node.The average degree of virtual channel multiplexing is computed by the GE/G/1/V queueing system with finite buffer capacity.We compare analytical results of message latency with those obtained through the simulation experiments in order to validate the accuracy of the derived model.

  13. Disease Mutations in the Ryanodine Receptor Central Region: Crystal Structures of a Phosphorylation Hot Spot Domain

    Energy Technology Data Exchange (ETDEWEB)

    Yuchi, Zhiguang; Lau, Kelvin; Van Petegem, Filip (UBC)

    2015-02-09

    Ryanodine Receptors (RyRs) are huge Ca{sup 2+} release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain salt bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.

  14. Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

    Science.gov (United States)

    Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; Sangster, T. C.; Betti, R.; Bose, A.; Boehly, T. R.; Bonino, M. J.; Campbell, E. M.; Cao, D.; Collins, T. J. B.; Craxton, R. S.; Davis, A. K.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Forrest, C. J.; Frenje, J. A.; Froula, D. H.; Gatu Johnson, M.; Glebov, V. Yu.; Harding, D. R.; Hohenberger, M.; Hu, S. X.; Jacobs-Perkins, D.; Janezic, R.; Karasik, M.; Keck, R. L.; Kelly, J. H.; Kessler, T. J.; Knauer, J. P.; Kosc, T. Z.; Loucks, S. J.; Marozas, J. A.; Marshall, F. J.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Michel, D. T.; Myatt, J. F.; Obenschain, S. P.; Petrasso, R. D.; Radha, P. B.; Rice, B.; Rosenberg, M. J.; Schmitt, A. J.; Schmitt, M. J.; Seka, W.; Shmayda, W. T.; Shoup, M. J.; Shvydky, A.; Skupsky, S.; Solodov, A. A.; Stoeckl, C.; Theobald, W.; Ulreich, J.; Wittman, M. D.; Woo, K. M.; Yaakobi, B.; Zuegel, J. D.

    2016-07-01

    A record fuel hot-spot pressure Phs=56 ±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ˜60 % of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

  15. The Satah Mountain and Baldface Mountain volcanic fields: Pleistocene hot spot volcanism in the Anahim Volcanic Belt, west-central British Columbia, Canada

    Science.gov (United States)

    Kuehn, Christian; Guest, Bernard; Russell, James K.; Benowitz, Jeff A.

    2015-03-01

    The Satah Mountain and Baldface Mountain volcanic fields (SMVF, BMVF) comprise more than three dozen small volcanic centers and erosional remnants thereof. These fields are located in the Chilcotin Highland of west-central British Columbia, Canada, and are spatially associated with the Anahim Volcanic Belt (AVB), a linear feature of alkaline to peralkaline plutonic and volcanic centers of Miocene to Holocene ages. The AVB has been postulated to be the track of a hot spot passing beneath the westward moving Cordilleran lithosphere. We test the AVB hot spot model by applying whole-rock 40Ar/39Ar geochronology ( n = 24) and geochemistry. Whole-rock chemical compositions of volcanic rock samples ( n = 59) from these two fields suggest a strong geochemical affinity with the nearby Itcha Range shield volcano; however, SMVF and BMVF centers are mostly small in volume (interaction of the potential hot spot with (pre)existing fracture systems in vicinity of the Itcha Range.

  16. Collective excitation of plasmonic hot-spots for enhanced hot charge carrier transfer in metal/semiconductor contacts

    Science.gov (United States)

    Piot, Adrien; Earl, Stuart K.; Ng, Charlene; Dligatch, Svetlana; Roberts, Ann; Davis, Timothy J.; Gómez, Daniel E.

    2015-04-01

    We show how a combination of near- and far-field coupling of the localised surface plasmon resonances in aluminium nanoparticles deposited on TiO2 films greatly enhances the visible light photocatalytic activity of the semiconductor material. We demonstrate two orders of magnitude enhancement in the rate of decomposition of methylene blue under visible light illumination when the surface of TiO2 films is decorated with gratings of Al nanoparticle dimers.We show how a combination of near- and far-field coupling of the localised surface plasmon resonances in aluminium nanoparticles deposited on TiO2 films greatly enhances the visible light photocatalytic activity of the semiconductor material. We demonstrate two orders of magnitude enhancement in the rate of decomposition of methylene blue under visible light illumination when the surface of TiO2 films is decorated with gratings of Al nanoparticle dimers. Electronic supplementary information (ESI) available: Detailed information on estimates of hot-electron injection efficiencies, electrodynamic simulations, sample preparation, spectroscopic and structural characterization and photocatalytic experiments. See DOI: 10.1039/c5nr01592h

  17. Professional- Amateur Astronomer Partnerships in Scientific Research: The Re-emergence of Jupiter's 5-Micron Hot Spots

    Science.gov (United States)

    Yanamandra-Fisher, P. A.

    2012-12-01

    The night sky, with all its delights and mysteries, enthrall professional and amateur astronomers alike. The discrete data sets acquired by professional astronomers via their approved observing programs at various national facilities are supplemented by the nearly daily observations of the same celestial object by amateur astronomers around the world. The emerging partnerships between professional and dedicated amateur astronomers rely on creating a niche for long timeline of multispectral remote sensing. "Citizen Astronomy" can be thought of as the paradigm shift transforming the nature of observational astronomy. In the past decade, it is the collective observations and their analyses by the ever-increasing global network of amateur astronomers that has discovered interesting phenomena and provided the reference backdrop for observations by ground-based professional astronomers and spacecraft missions. We shall present results from our collaborations to observe the recent global upheaval on Jupiter for the past five years and illustrate the strong synergy between the two groups. Global upheavals on Jupiter involve changes in the albedo of entire axisymmetric regions, lasting several years, with the last two occurring in 1989 and 2006. Against this backdrop of planetary-scale changes, discrete features such as the Great Red Spot (GRS), and other vortices exhibit changes on shorter spatial- and time-scales. One set of features we are currently tracking is the variability of the discrete equatorial 5-μm hot spots, semi-evenly spaced in longitude and confined to a narrow latitude band centered at 6.5°N (southern edge of the North Equatorial Belt, NEB), abundant in Voyager images (1980-1981). Tantalizingly similar patterns were observed in the visible (bright plumes and blue-gray regions), where reflectivity in the red is anti-correlated with 5-μm thermal radiance. During the recent NEB fade (2011 - early 2012), however, these otherwise ubiquitous features were

  18. Spallation as a dominant source of pusher-fuel and hot-spot mix in inertial confinement fusion capsules

    International Nuclear Information System (INIS)

    We suggest that a potentially dominant but previously neglected source of pusher-fuel and hot-spot ''mix'' may have been the main degradation mechanism for fusion energy yields of modern inertial confinement fusion (ICF) capsules designed and fielded to achieve high yields – not hydrodynamic instabilities. This potentially dominant mix source is the spallation of small chunks or ''grains'' of pusher material into the fuel regions whenever (1) the solid material adjacent to the fuel changes its phase by nucleation, and (2) this solid material spalls under shock loading and sudden decompression. Finally, we describe this mix mechanism, support it with simulations and experimental evidence, and explain how to eliminate it and thereby allow higher yields for ICF capsules and possibly ignition at the National Ignition Facility

  19. A Hot Spot and Mass Transfer of the Algol-type Binary System WZ Crv

    CERN Document Server

    Virnina, Natalia A; Mogorean, Maxim V

    2011-01-01

    We present the results of two color VR observation of the Algol-type binary system WZ Crv (12h44m15.19s, -21d25m35.4s) which were obtained using the remotely controlled telescope TOA-150 of Tzec Maun Observatory. We determined the moments of individual minima, the orbital period and its derivative, the initial epoch, color indices V-R and temperature estimates of the components. Also we noticed that the phase curve is asymmetric: the second maximum is higher than the first one. It indicates that there is a spot in the photosphere of one of the stars in this system.

  20. Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

    Science.gov (United States)

    Zhu, Limei; Peigneur, Steve; Gao, Bin; Zhang, Shangfei; Tytgat, Jan; Zhu, Shunyi

    2016-08-01

    Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity. PMID:27189560

  1. Infrared radiation emitted due to scanning of a hot spot as a probe of hidden defects

    Science.gov (United States)

    Woźny, Mariusz; Maś, Kinga; Prokhorenko, Serhiy; Ploch, Dariusz; Sheregii, E. M.

    2016-05-01

    Specially created subsurface defects in a sample are detected using a high resolution infrared camera FLIR SC7000. A scanning hot air (about 110 °C) nozzle is applied to introduce additional energy in a researched sample. The hidden defect has an increased temperature in comparison with the surrounding area that is a result of changed emissivity and thermal diffusivity. The suggested method is compared with pulse thermography which uses a xenon lamp for excitation.

  2. Liquid Metal Embrittlement in Resistance Spot Welding and Hot Tensile Tests of Surface-refined TWIP Steels

    Science.gov (United States)

    Barthelmie, J.; Schram, A.; Wesling, V.

    2016-03-01

    Automotive industry strives to reduce vehicle weight and therefore fuel consumption and carbon dioxide emissions. Especially in the auto body, material light weight construction is practiced, but the occupant safety must be ensured. These requirements demand high-strength steels with good forming and crash characteristics. Such an approach is the use of high- manganese-content TWIP steels, which achieve strengths of around 1,000 MPa and fracture strains of more than 60%. Welding surface-refined TWIP steels reduces their elongation at break and produces cracks due to the contact with liquid metal and the subsequent liquid metal embrittlement (LME). The results of resistance spot welds of mixed joints of high-manganese- content steel in combination with micro-alloyed ferritic steel and hot tensile tests are presented. The influence of different welding parameters on the sensitivity to liquid metal embrittlement is investigated by means of spot welding. In a high temperature tensile testing machine, the influence of different parameters is determined regardless of the welding process. Defined strains just below or above the yield point, and at 25% of elongation at break, show the correlation between the applied strain and liquid metal crack initiation. Due to the possibility to carry out tensile tests on a wide range of temperatures, dependencies of different temperatures of the zinc coating to the steel can be identified. Furthermore, the attack time of the zinc on the base material is investigated by defined heating periods.

  3. 40 CFR 93.123 - Procedures for determining localized CO, PM10, and PM2.5 concentrations (hot-spot analysis).

    Science.gov (United States)

    2010-07-01

    ... CO, PM10, and PM2.5 concentrations (hot-spot analysis). 93.123 Section 93.123 Protection of.... or the Federal Transit Laws § 93.123 Procedures for determining localized CO, PM10, and PM2.5... (“Localized CO, PM10, and PM2.5 violations”) must be based on quantitative analysis using the applicable...

  4. WLAN Hot Spot services for the automotive and oil industries :a business analysis Or : "Refuel the car with petrol and information, both ways at the gas station"

    NARCIS (Netherlands)

    L-F. Pau (Louis-François); M.H.P. Oremus

    2003-01-01

    textabstractWhile you refuel for gas ,why not refuel for information or download vehicle data ? This paper analyzes in extensive detail the user segmentation by vehicle usage , service offering , and full business models from WLAN hot spot services delivered to vehicles (private, professional , publ

  5. Quantitative Selective PCR of 16S Ribosomal DNA Correlates Well with Selective Agar Plating in Describing Population Dynamics of Indigenous Pseudomonas spp. in Soil Hot Spots

    OpenAIRE

    Johnsen, Kaare; Enger, Øivind; Jacobsen, Carsten S.; Thirup, Laila; Torsvik, Vigdis

    1999-01-01

    We used a quantitative PCR method targeting 16S ribosomal DNA using competitive PCR for specific detection of indigenous Pseudomonas DNA in soil hot spots. The amount of Pseudomonas DNA corresponded to the number of culturable Pseudomonas bacteria on Gould’s S1 agar. This represents the first use of PCR for quantification of indigenous bacteria in more than one sample of soil.

  6. Selecting optimal parallel microchannel configurations for active hot spot mitigation of multicore microprocessors in real time

    CERN Document Server

    Maganti, Lakshmi Sirisha; Sundararajan, T; Das, Sarit K

    2016-01-01

    Design of effective micro cooling systems to address the challenges of ever increasing heat flux from microdevices requires deep examination of real time problems and has been tackled in depth. The most common and apparently misleading assumption while designing micro cooling systems is that the heat flux generated by the device is uniform, but the reality is far from this. Detailed simulations have been performed by considering non uniform heat load employing the configurations U, I, Z for parallel microchannel systems with water and nanofluids as the coolants. An Intel Core i7 4770 3.40 GHz quad core processor has been mimicked using heat load data retrieved from a real microprocessor with non-uniform core activity. The study clearly demonstrates that there is a non-uniform thermal load induced temperature maldistribution along with the already existent flow maldistribution induced temperature maldistribution. The suitable configuration(s) for maximum possible overall heat removal for a hot zone while maxim...

  7. A spatial analysis of population dynamics and climate change in Africa: potential vulnerability hot spots emerge where precipitation declines and demographic pressures coincide

    Science.gov (United States)

    López-Carr, David; Pricope, Narcisa G.; Aukema, Juliann E.; Jankowska, Marta M.; Funk, Christopher C.; Husak, Gregory J.; Michaelsen, Joel C.

    2014-01-01

    We present an integrative measure of exposure and sensitivity components of vulnerability to climatic and demographic change for the African continent in order to identify “hot spots” of high potential population vulnerability. Getis-Ord Gi* spatial clustering analyses reveal statistically significant locations of spatio-temporal precipitation decline coinciding with high population density and increase. Statistically significant areas are evident, particularly across central, southern, and eastern Africa. The highly populated Lake Victoria basin emerges as a particularly salient hot spot. People located in the regions highlighted in this analysis suffer exceptionally high exposure to negative climate change impacts (as populations increase on lands with decreasing rainfall). Results may help inform further hot spot mapping and related research on demographic vulnerabilities to climate change. Results may also inform more suitable geographical targeting of policy interventions across the continent.

  8. Juan Fernández Ridge (Nazca Plate): petrology and thermochronology of a rejuvenated hot spot trail

    Science.gov (United States)

    Reyes, J.; Lara, L. E.

    2012-04-01

    The Juan Fernández Ridge on the oceanic Nazca plate is thought to be a classic hot spot trail because of the apparent westward rejuvenation of the eruptive ages. However, geochronological data is still scarce and there are a few constrains to support this hypothesis like the ca. 9 Ma Ar-Ar age of the O'Higgins seamount (115 km from the Chile-Perú trench), some published K-Ar ages of ca. 3-4 Ma in Robinson Crusoe island (580 km from the trench) and ca. 1 Ma in Alejandro Selkirk (180 km further west). New reconnaissance K-Ar ages and specially the ongoing Ar-Ar dating effort in Robinson Crusoe define a ca. 1-4 Ma time span, which partially overlap with the age of Alejandro Selkirk, breaking the expected age progression given that the Nazca plate moves eastwards at ca. 6-8 cm/yr. In addition, new geological mapping shows a sharp unconformity between the older (ca. 4 Ma), strongly altered sequences and the more recent (ca. 1 Ma), post-erosional volcanic piles, where the proximal facies are still preserved. Petrological evidence also supports this evolution pattern. In fact, the partially altered older sequence is tholeiitic (Ba/Yb=12.70; La/Yb=8.12; Ba/Y=6.51; Ba/Zr=0.89). The shield stage (ca. 1-3 Ma) is transicional from tholeiitic to alkaline (Ba/Yb=18.07-8.32; La/Yb=4.59-9.84; Ba/Y=4.24-8.18; Ba/Zr=0.73-1.09) and the younger (ca. 1 Ma) is mostly alkaline (Ba/Yb=38.15; La/Yb=15.66; Ba/Y=20.27; Ba/Zr=2.31). A fixed deep-mantle plume origin for Pacific hot spots has been widely debated and concurrent phenomena arose as a possible explanation for non-linear age progressions and/or long-lived volcanic activity. In fact, intraplate regional tectonics, plume displacement, and mantle heterogeneities could be the main factor of the ridge architecture or the mask for a first-order linear trend. An ongoing mapping and dating effort is aimed to understand the evolution of the Juan Fernández Ridge, testing the main hypothesis. This research is supported by FONDECYT Project

  9. Can we detect hot/cold spots in the CMB with Minkowski Functionals?

    International Nuclear Information System (INIS)

    In this paper, we investigate the utility of Minkowski Functionals as a probe of cold/hot disk-like structures in the CMB. In order to construct an accurate estimator, we resolve a long-standing issue with the use of Minkowski Functionals as probes of the CMB sky — namely that of systematic differences (''residuals'') when numerical and analytical MF are compared. We show that such residuals are in fact by-products of binning, whereas it was originally attributed to pixelation or masking effects. We then derive a map-independent estimator that encodes the effects of binning, applicable to beyond our present work. Using this residual-free estimator, we show that small disk-like effects (as claimed by Vielva et al. [1,2]) can be detected only when a large sample of such maps are averaged over. In other words, our estimator is noise-dominated for small disk sizes at WMAP resolution. To confirm our suspicion, we apply our estimator to the WMAP7 data to obtain a null result

  10. Can we detect hot/cold spots in the CMB with Minkowski Functionals?

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Eugene A. [Institute for Strings, Cosmology and Astroparticle Physics, Columbia University, New York, 10027 NY (United States); Simon, Dennis, E-mail: eugene.a.lim@gmail.com, E-mail: dsimon@astro.uni-wuerzburg.de [Institut für Theoretische Physik und Astrophysik, Julius-Maximilians-Universität Würzburg, D-97074 Würzburg (Germany)

    2012-01-01

    In this paper, we investigate the utility of Minkowski Functionals as a probe of cold/hot disk-like structures in the CMB. In order to construct an accurate estimator, we resolve a long-standing issue with the use of Minkowski Functionals as probes of the CMB sky — namely that of systematic differences (''residuals'') when numerical and analytical MF are compared. We show that such residuals are in fact by-products of binning, whereas it was originally attributed to pixelation or masking effects. We then derive a map-independent estimator that encodes the effects of binning, applicable to beyond our present work. Using this residual-free estimator, we show that small disk-like effects (as claimed by Vielva et al. [1,2]) can be detected only when a large sample of such maps are averaged over. In other words, our estimator is noise-dominated for small disk sizes at WMAP resolution. To confirm our suspicion, we apply our estimator to the WMAP7 data to obtain a null result.

  11. Demonstration of 55 +/- 7-Gbar Hot-Spot Pressure in Direct-Drive Layered DT Cryogenic Implosions on OMEGA

    Science.gov (United States)

    Regan, S. P.

    2015-11-01

    Direct-drive ignition target designs for the National Ignition Facility (NIF) require hot-spot pressures in excess of 100 Gbar. Only one-third of the required pressure was inferred in earlier experimental campaigns conducted on the 60-beam, 30-kJ, 351-nm OMEGA laser with direct-drive implosions of layered DT cryogenic targets. Laser and target improvements were implemented on OMEGA to increase the stagnation pressure, including a set of phase plates to increase the laser irradiation uniformity on target and a purified fuel with isotope composition reaching a 50:50 DT ratio. Diagnostic improvements were made for a neutron burnwidth measurement with a 40-ps impulse response and a 16-channel Kirkpatrick-Baez microscope to measure gated (30-ps) x-ray images of the core near peak compression with 6- μm resolution. The inferred volume-averaged, peak pressure in the current campaign almost doubled to 55 +/- 7 Gbar with a neutron yield approaching 5 ×1013 . Further target performance improvements to reach hydrodynamic equivalence to ignition on OMEGA require mitigation of cross-beam energy transfer (CBET), which reduces the laser coupling. A proposed technique to reduce CBET by driving the spherical target with overlapping laser beams having individual focal spots smaller than the outside diameter of the target was investigated. The diameter of the target was discretely varied from 800 to 1000 μm, while the laser focal spot size was kept constant at 820 μm. The larger targets driven with up to 30 kJ of laser energy used dynamic bandwidth reduction, where the smoothing by spectral dispersion (SSD) is only applied to the pickets. The smaller targets driven with 26 kJ of laser energy had SSD on the entire pulse. This talk will summarize the results of this CBET mitigation campaign and describe a path forward to achieve ignition hydro-equivalence on OMEGA. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under

  12. Hot Spot Induced Cenozoic Volcanism in the Upper Rajang Valley, Sarawak - Is Borneo Rifting?

    Science.gov (United States)

    Taib, N.

    2010-12-01

    The Upper Rajang Valley covers a large area in the northern interior of the island of Borneo, in the Malaysian state of Sarawak . It is underlain by the Cretaceous to Late Eocene deep to shallow marine sediments of the Rajang Group. Within this area are several Cenozoic volcanic edifices, which to date have been sparsely studied. Two distinct episodes of volcanism are recognized - the first, dated early Eocene, consists of K-rich basalts, and is represented by the Bukit Mersing volcanics, which were erupted conformably onto deep water turbidites of the Rajang Group. The second, far more extensive, is dated Pliocene to Quaternary, and is bimodal, consisting mainly of early dacite and rhyodacite tuffs, with a smaller amount of later basalt, forming several volcanic plateaus and massifs (Hose Mountains, Usun Apau, Linau-Balui, Nieuwenhuis Mountains and others). They lie unconformably over pre-Miocene sediments, the Linau-Balui basalts having been erupted onto Quaternary river terraces. Mantle-normalized REE and incompatible trace element spider plots reveal that the Bukit Mersing basalts have geochemical affinity with Oceanic Island Basalts (OIB) and rift basalts, being enriched in LREEs and Most Incompatible Elements, and no Eu anomaly. Preliminary trace element data for several basalt samples from Usun Apau also show Oceanic Island/Rift affinity. Bimodal volcanism is most often associated with rift environments. Efforts are being made to radiometrically date the volcanics, in part to determine the possibility of future eruptions. The Upper Rajang Valley is remote, covered in tropical rainforest and is very sparsely populated. At this time, there is no information concerning signs of imminent volcanism, such as hot springs and microseismicity.

  13. From science into practice: modelling hot spots for corporate flood risk and emergency management with high-resolution digital terrain data

    Science.gov (United States)

    Pfurtscheller, Clemens; Vetter, Michael; Werthmann, Markus

    2010-05-01

    In times of increasing scarcity of private or public resources and uncertain changes in natural environment caused by climate variations, prevention and risk management against floods and coherent processes in mountainous regions, like debris flows or log jams, should be faced as a main challenge for globalised enterprises whose production facilities are located in flood-prone areas. From an entrepreneurial perspective, vulnerability of production facilities which causes restrictions or a total termination of production processes has to be optimised by means of cost-benefit-principles. Modern production enterprises are subject to globalisation and accompanying aspects, like short order and delivery periods, interlinking production processes and just-in-time manufacturing, so a breakdown of production provokes substantial financial impacts, unemployment and a decline of gross regional product. The aim of the presented project is to identify weak and critical points of the corporate emergency planning ("hot spots") and to assess possible losses triggered by mountainous flood processes using high-resolution digital terrain models (DTM) from airborne LiDAR (ALS). We derive flood-hot spots and model critical locations where the risk of natural hazards is very high. To model those hot spots a flood simulation based on an ALS-DTM has to be calculated. Based on that flood simulation, the flood heights of the overflowed locations which are lower than a threshold are mapped as flood-hot-spots. Then the corporate critical infrastructure, e.g. production facilities or lifelines, which are affected by the flooding, can be figured out. After the identification of hot spots and possible damage potential, the implementation of the results into corporate risk and emergency management guarantees the transdisciplinary approach involving stakeholders, risk and safety management officers and corporate fire brigade. Thus, the interdisciplinary analysis, including remote sensing

  14. The Hot Spot Analysis: Utilization as Customized Management Tool towards Sustainable Value Chains of Companies in the Food Sector

    Directory of Open Access Journals (Sweden)

    H. Rohn

    2014-12-01

    Full Text Available The food and agricultural sector will face numerous challenges in the next decades, arising from changing global production and consumption patterns, which currently go along with high resource use, causing ecological and socio-economic impacts. The aim of this paper is to illustrate and evaluate the practical applicability of the Hot Spot Analysis methodology in the context of supply chain management in companies. The HSA is a method to identify social and ecological problems along the entire life cycle of a product. Special emphasis is put on a customized implementation in the value chain beef of McDonald’s Germany. The HSA of McDonald’s beef value chain shows that the main ecological problems arise in the phase of raw material extraction, whereas the main social problems can be identified in the phase of slaughtering. Finally, the paper shows potentials and shortcomings of such a customized application and how the results can be implemented in the sustainability management of a company.

  15. Septic systems as hot-spots of pollutants in the environment: Fate and mass balance of micropollutants in septic drainfields.

    Science.gov (United States)

    Yang, Yun-Ya; Toor, Gurpal S; Wilson, P Chris; Williams, Clinton F

    2016-10-01

    Septic systems, a common type of onsite wastewater treatment systems, can be an important source of micropollutants in the environment. We investigated the fate and mass balance of 17 micropollutants, including wastewater markers, hormones, pharmaceuticals and personal care products (PPCPs) in the drainfield of a septic system. Drainfields were replicated in lysimeters (1.5m length, 0.9m width, 0.9m height) and managed similar to the field practice. In each lysimeter, a drip line dispersed 9L of septic tank effluent (STE) per day (equivalent to 32.29L/m(2) per day). Fourteen micropollutants in the STE and 12 in the leachate from drainfields were detected over eight months. Concentrations of most micropollutants in the leachate were low (85% of the added micropollutants except for sucralose were attenuated in the drainfield. We discovered that sorption was the key mechanism for retention of carbamazepine and partially for sulfamethoxazole, whereas microbial degradation likely attenuated acetaminophen in the drainfield. This data suggests that sorption and microbial degradation limited transport of micropollutants from the drainfields. However, the leaching of small amounts of micropollutants indicate that septic systems are hot-spots of micropollutants in the environment and a better understanding of micropollutants in septic systems is needed to protect groundwater quality. PMID:27312276

  16. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  17. Improving the hot-spot pressure and demonstrating ignition hydrodynamic equivalence in cryogenic deuterium tritium implosions on OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Goncharov, V. N. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Sangster, T. C. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Betti, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Boehly, T. R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Bonino, M. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Collins, T. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Craxton, R. S. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Delettrez, J. A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Edgell, D. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Epstein, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Follett, R. K. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Forrest, C. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Froula, D. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Yu. Glebov, V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Harding, D. R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Henchen, R. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Hu, S. X. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Igumenshchev, I. V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Janezic, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kelly, J. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kessler, T. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kosc, T. Z. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Loucks, S. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Marozas, J. A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Marshall, F. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Maximov, A. V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; McCrory, R. L. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; McKenty, P. W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Meyerhofer, D. D. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Michel, D. T. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Myatt, J. F. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Nora, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Radha, P. B. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Regan, S. P. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Seka, W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Shmayda, W. T. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Short, R.W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Shvydky, A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Skupsky, S. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Stoeckl, C. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Yaakobi, B. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Frenje, J. A. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Gatu-Johnson, M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Petrasso, R. D. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Casey, D. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-05-01

    Reaching ignition in direct-drive (DD) inertial confinement fusion implosions requires achieving central pressures in excess of 100 Gbar. The OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] is used to study the physics of implosions that are hydrodynamically equivalent to the ignition designs on the National Ignition Facility (NIF) [J. A. Paisner et al., Laser Focus World 30, 75 (1994)]. It is shown that the highest hot-spot pressures (up to 40 Gbar) are achieved in target designs with a fuel adiabat of α ≅ 4, an implosion velocity of 3.8 × 10⁷ cm/s, and a laser intensity of ~10¹⁵ W/cm². These moderate-adiabat implosions are well understood using two-dimensional hydrocode simulations. The performance of lower-adiabat implosions is significantly degraded relative to code predictions, a common feature between DD implosions on OMEGA and indirect-drive cryogenic implosions on the NIF. Simplified theoretical models are developed to gain physical understanding of the implosion dynamics that dictate the target performance. These models indicate that degradations in the shell density and integrity (caused by hydrodynamic instabilities during the target acceleration) coupled with hydrodynamics at stagnation are the main failure mechanisms in low-adiabat designs. To demonstrate ignition hydrodynamic equivalence in cryogenic implosions on OMEGA, the target-design robustness to hydrodynamic instability growth must be improved by reducing laser-coupling losses caused by cross beam energy transfer.

  18. Stabilization of large drainage basins over geological time scales: Cenozoic West Africa, hot spot swell growth, and the Niger River

    Science.gov (United States)

    Chardon, Dominique; Grimaud, Jean-Louis; Rouby, Delphine; Beauvais, Anicet; Christophoul, Frédéric

    2016-03-01

    Reconstructing the evolving geometry of large river catchments over geological time scales is crucial to constraining yields to sedimentary basins. In the case of Africa, it should further help deciphering the response of large cratonic sediment routing systems to Cenozoic growth of the basin-and-swell topography of the continent. Mapping of dated and regionally correlated lateritic paleolandscape remnants complemented by onshore sedimentological archives allows the reconstruction of two physiographic configurations of West Africa in the Paleogene. Those reconstructions show that the geometry of the drainage is stabilized by the late early Oligocene (29 Ma) and probably by the end of the Eocene (34 Ma), allowing to effectively link the inland morphoclimatic record to offshore sedimentation since that time, particularly in the case of the Niger catchment—delta system. Mid-Eocene paleogeography reveals the antiquity of the Senegambia catchment back to at least 45 Ma and suggests that a marginal upwarp forming a continental divide preexisted early Oligocene connection of the Niger and Volta catchments to the Equatorial Atlantic Ocean. Such a drainage rearrangement was primarily enhanced by the topographic growth of the Hoggar hot spot swell and caused a stratigraphic turnover along the Equatorial margin of West Africa.

  19. Identifying and Mitigating Potential Nutrient and Sediment Hot Spots under a Future Scenario in the Missouri River Basin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, May [Argonne National Lab. (ANL), Argonne, IL (United States); Zhang, Zhonglong [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    clearly attributable to the conversion of a large amount of land to switchgrass. The Middle Lower Missouri River and Lower Missouri River were identified as hot regions. Further analysis identified four subbasins (10240002, 10230007, 10290402, and 10300200) as being the most vulnerable in terms of sediment, nitrogen, and phosphorus loadings. Overall, results suggest that increasing the amount of switchgrass acreage in the hot spots should be considered to mitigate the nutrient loads. The study provides an analytical method to support stakeholders in making informed decisions that balance biofuel production and water sustainability.

  20. Hot Spots and Hot Moments of Methylmercury Production Associated With Agricultural and Non-agricultural Wetlands of the Yolo Bypass Wildlife Area, California

    Science.gov (United States)

    Marvin-Dipasquale, M.; Windham-Myers, L.; Agee, J. L.; Kakouros, E.; Cox, M. H.; Fleck, J.; Alpers, C. N.; Stephenson, M.

    2008-12-01

    The Yolo Bypass Wildlife Area (YBWA) is part of the larger Yolo Bypass floodwater protection zone associated with the Sacramento River and the Sacramento-San Joaquin Delta, in California. While mercury contamination is widespread throughout the region due to historic mining practices, the Yolo Bypass is responsible for a high proportion of the aqueous methylmercury (MeHg) entering the Delta, and biota from the Yolo Bypass are particularly elevated in toxic MeHg. Land use in the YBWA includes seasonally flooded agricultural fields (white rice, wild rice, fallow fields), and permanently and seasonally flooded non-agricultural wetlands used for resident and migratory waterfowl. Mercury biogeochemistry was examined in 0-2 cm surface sediment, as a function of habitat type, wetland management, and agricultural practices during the 2007-08 crop year. In permanently flooded wetlands, MeHg concentrations varied within a narrow range (ca. 0.5-1.5 ng/g dry wt) throughout the study period. In contrast, the three types of agricultural fields had higher MeHg concentrations throughout the rice-growing season (June-Sept; ca. 1.5-3.5 ng/g), and exhibited the highest levels (ca. 3.3-6.3 ng/g) in the post-harvest winter period (Dec-Feb). Further, naturally dried sediment, sampled during July '08 from post-harvest drained fallow agricultural fields (prior to reflooding) had MeHg concentrations that were also quite elevated (3.1 +/- 1.5 ng/g). This suggests that the initial elevated concentrations of overlying water MeHg, sometimes measured soon after flooding previously dried fields, may be related to the release of MeHg formed during the previous wet season and trapped in dried sediment, as opposed to being MeHg newly produced by bacteria upon soil rewetting. These results indicate that the 'hot spots and hot moments' associated with MeHg production in this system are linked to hydrologic manipulations (wetting and drying) in the agricultural fields, and that the practice of post

  1. The Design of LGP to Improve the Hot Spot Phenomenon in Edge-lit Mode LED Backlight%改善侧导光LED背光Hot Spot现象的导光板设计

    Institute of Scientific and Technical Information of China (English)

    金海洋; 刘卫东; 乔明胜

    2011-01-01

    就改善侧导光LED背光Hot Spot现象,文章提出了一种解决办法:在导光板入光侧对应LED的位置进行处理,让其形成一个非球面的凹面,可以使LED发出的光发散,从而减轻或消除Hot Spot现象。%In order to improve the Hot Spot phenomenon in Edge LED Backlight Unit,we puts forward a kind of solution: Do some processing at position of LED on LGP to let it forming a Asphere surface.This model can make light divergent,so can relieve or eliminate Hot

  2. Mapping Publication Trends and Identifying Hot Spots of Research on Internet Health Information Seeking Behavior: A Quantitative and Co-Word Biclustering Analysis

    OpenAIRE

    Li, Fan; Min LI; Guan, Peng; Ma, Shuang; Cui, Lei

    2015-01-01

    Background The Internet has become an established source of health information for people seeking health information. In recent years, research on the health information seeking behavior of Internet users has become an increasingly important scholarly focus. However, there have been no long-term bibliometric studies to date on Internet health information seeking behavior. Objective The purpose of this study was to map publication trends and explore research hot spots of Internet health inform...

  3. Do we miss the hot spots? – The use of very high resolution aerial photographs to quantify carbon fluxes in peatlands

    Directory of Open Access Journals (Sweden)

    B. Thees

    2008-03-01

    Full Text Available Accurate determination of carbon balances in heterogeneous ecosystems often requires the extrapolation of point based measurements. The ground resolution (pixel size of the extrapolation base, e.g. a land-cover map, might thus influence the calculated carbon balance, in particular if biogeochemical hot spots are small in size. In this paper, we test the effects of varying ground resolution on the calculated carbon balance of a boreal peatland consisting of hummocks (dry, lawns (intermediate and flarks (wet surfaces. The generalizations in lower resolution imagery led to biased area estimates for individual micro-site types. While areas of lawns and hummocks were stable below a threshold resolution of ~60 cm, the maximum of the flark area was located at resolutions below 25 cm and was then decreasing with coarsening resolution. Using a resolution of 100 cm instead of 6 cm led to an overestimation of total CO2 uptake of the studied peatland area (approximately 14 600 m2 of ~6% and an underestimation of total CH4 emission of ~11%. To accurately determine the surface area of scattered and small-sized micro-site types in heterogeneous ecosystems (e.g. flarks in peatlands, a minimum ground resolution appears necessary. In our case this leads to a recommended resolution of 25 cm, which can be derived by conventional airborne imagery. The usage of high resolution imagery from commercial satellites, e.g. Quickbird, however, is likely to underestimate the surface area of biogeochemical hot spots. It is important to note that the observed resolution effect on the carbon balance estimates can be much stronger for other ecosystems than for the investigated peatland where the relative hot spot area of the flarks is very small and their hot spot characteristics with respect to CH4 and CO2 fluxes is rather modest.

  4. Do we miss the hot spots? – The use of very high resolution aerial photographs to quantify carbon fluxes in peatlands

    Directory of Open Access Journals (Sweden)

    T. Becker

    2008-10-01

    Full Text Available Accurate determination of carbon balances in heterogeneous ecosystems often requires the extrapolation of point based measurements. The ground resolution (pixel size of the extrapolation base, e.g. a land-cover map, might thus influence the calculated carbon balance, in particular if biogeochemical hot spots are small in size. In this paper, we test the effects of varying ground resolution on the calculated carbon balance of a boreal peatland consisting of hummocks (dry, lawns (intermediate and flarks (wet surfaces. The generalizations in lower resolution imagery led to biased area estimates for individual micro-site types. While areas of lawns and hummocks were stable below a threshold resolution of ~60 cm, the maximum of the flark area was located at resolutions below 25 cm and was then decreasing with coarsening resolution. Using a resolution of 100 cm instead of 6 cm led to an overestimation of total CO2 uptake of the studied peatland area (approximately 14 600 m2 of ~5% and an underestimation of total CH4 emission of ~6%. To accurately determine the surface area of scattered and small-sized micro-site types in heterogeneous ecosystems (e.g. flarks in peatlands, a minimum ground resolution appears necessary. In our case this leads to a recommended resolution of 25 cm, which can be derived by conventional airborne imagery. The usage of high resolution imagery from commercial satellites, e.g. Quickbird, however, is likely to underestimate the surface area of biogeochemical hot spots. It is important to note that the observed resolution effect on the carbon balance estimates can be much stronger for other ecosystems than for the investigated peatland. In the investigated peatland the relative hot spot area of the flarks is very small and their hot spot characteristics with respect to CH4 and CO2 fluxes is rather modest.

  5. Bone Scan "Hot Spot" at the Superior Lateral Orbital Margin Fronto-zygomatic Suture Uptake Characterized with Tc-99m MDP SPECT/CT.

    Science.gov (United States)

    Thang, S P; Tan, A E H; Goh, A S W

    2011-07-01

    Findings of a solitary "hot spot" at the superior lateral orbital margin on bone scan scintigraphy is not uncommonly seen, and is often dismissed as a benign lesion. However, the exact etiology is indeterminate. We present two cases in which hybrid single photon emission computed tomography/computed tomography imaging was able to characterize and localize this uptake, demonstrating correlation to the right fronto-zygomatic suture.

  6. Established Companies meet Start-ups : Case: A service to research developing business models in start-up hot spots around the globe

    OpenAIRE

    Eisenblätter, Simon

    2016-01-01

    This thesis presents a business model with the aim to improve conversation between traditional companies and newly established start-ups. The assumption that such conversation can be facilitated by scouting for innovation in start-up hot spots around the world, will be discussed throughout the paper. The purpose of this work is to lay out a plan which can be presented to a first range of possible customers, with the goal of negotiating a trial cooperation. Before introducing the busi...

  7. Mobile Launch Platform Vehicle Assembly Building Area (SWMU 056) Hot Spot 3 Bioremediation Interim Measures Work Plan, Kennedy Space Center, Florida

    Science.gov (United States)

    Whitney L. Morrison; Daprato, Rebecca C.

    2016-01-01

    This Interim Measures Work Plan (IMWP) presents an approach and design for the remediation of chlorinated volatile organic compound (CVOC) groundwater impacts using bioremediation (biostimulation and bioaugmentation) in Hot Spot 3, which is defined by the area where CVOC (trichloroethene [TCE], cis-1,2-dichloroethene [cDCE], and vinyl chloride [VC]) concentrations are greater than 10 times their respective Florida Department of Environmental Protection (FDEP) Natural Attenuation Default Concentration (NADC) [10xNADC] near the western Mobile Launch Platform (MLP) structure. The IM treatment area is the Hot Spot 3 area, which is approximately 0.07 acres and extends from approximately 6 to 22 and 41 to 55 feet below land surface (ft BLS). Within Hot Spot 3, a source zone (SZ; area with TCE concentrations greater than 1% solubility [11,000 micrograms per liter (micrograms/L)]) was delineated and is approximately 0.02 acres and extends from approximately 6 to 16 and 41 to 50 ft BLS.

  8. Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

    Science.gov (United States)

    Regan, S P; Goncharov, V N; Igumenshchev, I V; Sangster, T C; Betti, R; Bose, A; Boehly, T R; Bonino, M J; Campbell, E M; Cao, D; Collins, T J B; Craxton, R S; Davis, A K; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Frenje, J A; Froula, D H; Gatu Johnson, M; Glebov, V Yu; Harding, D R; Hohenberger, M; Hu, S X; Jacobs-Perkins, D; Janezic, R; Karasik, M; Keck, R L; Kelly, J H; Kessler, T J; Knauer, J P; Kosc, T Z; Loucks, S J; Marozas, J A; Marshall, F J; McCrory, R L; McKenty, P W; Meyerhofer, D D; Michel, D T; Myatt, J F; Obenschain, S P; Petrasso, R D; Radha, P B; Rice, B; Rosenberg, M J; Schmitt, A J; Schmitt, M J; Seka, W; Shmayda, W T; Shoup, M J; Shvydky, A; Skupsky, S; Solodov, A A; Stoeckl, C; Theobald, W; Ulreich, J; Wittman, M D; Woo, K M; Yaakobi, B; Zuegel, J D

    2016-07-01

    A record fuel hot-spot pressure P_{hs}=56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

  9. Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

    Science.gov (United States)

    Regan, S P; Goncharov, V N; Igumenshchev, I V; Sangster, T C; Betti, R; Bose, A; Boehly, T R; Bonino, M J; Campbell, E M; Cao, D; Collins, T J B; Craxton, R S; Davis, A K; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Frenje, J A; Froula, D H; Gatu Johnson, M; Glebov, V Yu; Harding, D R; Hohenberger, M; Hu, S X; Jacobs-Perkins, D; Janezic, R; Karasik, M; Keck, R L; Kelly, J H; Kessler, T J; Knauer, J P; Kosc, T Z; Loucks, S J; Marozas, J A; Marshall, F J; McCrory, R L; McKenty, P W; Meyerhofer, D D; Michel, D T; Myatt, J F; Obenschain, S P; Petrasso, R D; Radha, P B; Rice, B; Rosenberg, M J; Schmitt, A J; Schmitt, M J; Seka, W; Shmayda, W T; Shoup, M J; Shvydky, A; Skupsky, S; Solodov, A A; Stoeckl, C; Theobald, W; Ulreich, J; Wittman, M D; Woo, K M; Yaakobi, B; Zuegel, J D

    2016-07-01

    A record fuel hot-spot pressure P_{hs}=56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance. PMID:27447511

  10. Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

    Science.gov (United States)

    Nakamura, Akinori; Fueki, Noboru; Shiba, Naoko; Motoki, Hirohiko; Miyazaki, Daigo; Nishizawa, Hitomi; Echigoya, Yusuke; Yokota, Toshifumi; Aoki, Yoshitsugu; Takeda, Shin'ichi

    2016-07-01

    Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene. PMID:27009627

  11. Multi-Scale Multi-physics Methods Development for the Calculation of Hot-Spots in the NGNP

    Energy Technology Data Exchange (ETDEWEB)

    Downar, Thomas [Univ. of Michigan, Ann Arbor, MI (United States); Seker, Volkan [Univ. of Michigan, Ann Arbor, MI (United States)

    2013-04-30

    Radioactive gaseous fission products are released out of the fuel element at a significantly higher rate when the fuel temperature exceeds 1600°C in high-temperature gas-cooled reactors (HTGRs). Therefore, it is of paramount importance to accurately predict the peak fuel temperature during all operational and design-basis accident conditions. The current methods used to predict the peak fuel temperature in HTGRs, such as the Next-Generation Nuclear Plant (NGNP), estimate the average fuel temperature in a computational mesh modeling hundreds of fuel pebbles or a fuel assembly in a pebble-bed reactor (PBR) or prismatic block type reactor (PMR), respectively. Experiments conducted in operating HTGRs indicate considerable uncertainty in the current methods and correlations used to predict actual temperatures. The objective of this project is to improve the accuracy in the prediction of local "hot" spots by developing multi-scale, multi-physics methods and implementing them within the framework of established codes used for NGNP analysis.The multi-scale approach which this project will implement begins with defining suitable scales for a physical and mathematical model and then deriving and applying the appropriate boundary conditions between scales. The macro scale is the greatest length that describes the entire reactor, whereas the meso scale models only a fuel block in a prismatic reactor and ten to hundreds of pebbles in a pebble bed reactor. The smallest scale is the micro scale--the level of a fuel kernel of the pebble in a PBR and fuel compact in a PMR--which needs to be resolved in order to calculate the peak temperature in a fuel kernel.

  12. Opening the research agenda for selection of hot spots for human biomonitoring research in Belgium: a participatory research project

    Directory of Open Access Journals (Sweden)

    Chovanova Hana

    2010-07-01

    Full Text Available Abstract Background In order to select priority hotspots for environment and health research in Flanders (Belgium, an open procedure was organized. Environment and health hotspots are strong polluting point sources with possible health effects for residents living in the vicinity of the hot spot. The selection procedure was part of the work of the Flemish Centre of Expertise for Environment and Health, which investigates the relation between environmental pollution and human health. The project is funded and steered by the Flemish government. Methods The involvement of other actors than merely experts is inspired by the 'analytical-deliberative' approach of the National Research Council in the United States and the extended peer community approach. These approaches stress the importance of involving different expert- and social perspectives in order to increase the knowledge base on complex issues. In the procedure used in the project a combination of expert and stakeholder input was essential. The final decision was supported by a multi-criteria analysis of expert assessment and stakeholder advice. Results The endeavour was challenging from the start because of the complicated ambition of including a diversity of actors, potential hotspots, concerns and assessment criteria, but nevertheless the procedure proved its value in both structuring and informing the decision-making process. Moreover the process gained the support of most actors participating in the process, even though the final selection could not satisfy all preferences. Conclusions Opening the research agenda exemplifies the value of inter- and transdisciplinary cooperation as well as the need for a well-structured and negotiated procedure that combines relevant factors and actors with pragmatism. The value of such a process also needs to prove itself in practice after the procedure has been completed: the tension between an ambition of openness on the one hand and a more closed

  13. The acetabular fossa hot spot on 18F-FDG PET/CT: epidemiology, natural history, and proposed etiology

    International Nuclear Information System (INIS)

    To describe a benign focus of increased activity in the acetabular fossa (the acetabular fossa hot spot, AFHS) on 18F-FDG PET/CT that can mimic a neoplasm. 18F-FDG PET/CT images from four patient populations were examined. Group 1 (n = 13) was collected from a search of radiology reports and used to define the AFHS and for hypothesis generation. Group 2 (n = 1,150) was used for prevalence of AFHS. Group 3 (n = 1,213) had PET/CT and MRI pelvis within a week of each other and was used to correlate metabolic and anatomic findings. Group 4 (n = 100) was used to generate the control group. Data were collected on demographics, common comorbidities, underlying cancer diagnosis and status, and hip symptoms. Prevalence of AFHS was 0.36 % (95 % CI 0.10-0.91 %). None progressed to malignancy or was associated with cancer status. The majority (71 %) were on the left, and 6 % were bilateral. Mean SUVmax of the AFHS was 4.8 (range, 2.7-7.8). Male patients were more likely to have the AFHS (OR = 8.69, 95 % CI 1.88-40.13). There was no difference with respect to other collected data, including hip symptoms. Average minimum duration of AFHS was 346 days (range, 50-1,010 days). Readers did not detect corresponding hip abnormalities on MRIs. AFHS is a benign finding that may be caused by subclinical ligamentum teres injury, focal synovitis, or degeneration of acetabular fossa fat. Despite uncertainty regarding its etiology, recognition of AFHS as a benign finding can prevent morbidity associated with unnecessary biopsy or initiation of therapy. (orig.)

  14. Improving the hot-spot pressure and demonstrating ignition hydrodynamic equivalence in cryogenic deuterium–tritium implosions on OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Goncharov, V. N.; Sangster, T. C.; Betti, R.; Boehly, T. R.; Bonino, M. J.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Follett, R. K.; Forrest, C. J.; Froula, D. H.; Glebov, V. Yu.; Harding, D. R.; Henchen, R. J.; Hu, S. X.; Igumenshchev, I. V.; Janezic, R.; Kelly, J. H. [Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623 (United States); and others

    2014-05-15

    Reaching ignition in direct-drive (DD) inertial confinement fusion implosions requires achieving central pressures in excess of 100 Gbar. The OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] is used to study the physics of implosions that are hydrodynamically equivalent to the ignition designs on the National Ignition Facility (NIF) [J. A. Paisner et al., Laser Focus World 30, 75 (1994)]. It is shown that the highest hot-spot pressures (up to 40 Gbar) are achieved in target designs with a fuel adiabat of α ≃ 4, an implosion velocity of 3.8 × 10{sup 7} cm/s, and a laser intensity of ∼10{sup 15} W/cm{sup 2}. These moderate-adiabat implosions are well understood using two-dimensional hydrocode simulations. The performance of lower-adiabat implosions is significantly degraded relative to code predictions, a common feature between DD implosions on OMEGA and indirect-drive cryogenic implosions on the NIF. Simplified theoretical models are developed to gain physical understanding of the implosion dynamics that dictate the target performance. These models indicate that degradations in the shell density and integrity (caused by hydrodynamic instabilities during the target acceleration) coupled with hydrodynamics at stagnation are the main failure mechanisms in low-adiabat designs. To demonstrate ignition hydrodynamic equivalence in cryogenic implosions on OMEGA, the target-design robustness to hydrodynamic instability growth must be improved by reducing laser-coupling losses caused by cross beam energy transfer.

  15. The acetabular fossa hot spot on {sup 18}F-FDG PET/CT: epidemiology, natural history, and proposed etiology

    Energy Technology Data Exchange (ETDEWEB)

    Kubicki, Shelby L. [Trinity University, San Antonio, TX (United States); Richardson, Michael L. [University of Washington, Department of Radiology, Seattle, WA (United States); Martin, Thomas [X-Ray Associates of New Mexico, Department of Radiology, Albuquerque, NM (United States); Rohren, Eric [The University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Radiology, Division of Nuclear Medicine, Houston, TX (United States); Wei, Wei [The University of Texas M.D. Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Amini, Behrang [The University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Radiology, Division of Musculoskeletal Radiology, Houston, TX (United States)

    2015-01-15

    To describe a benign focus of increased activity in the acetabular fossa (the acetabular fossa hot spot, AFHS) on {sup 18}F-FDG PET/CT that can mimic a neoplasm. {sup 18}F-FDG PET/CT images from four patient populations were examined. Group 1 (n = 13) was collected from a search of radiology reports and used to define the AFHS and for hypothesis generation. Group 2 (n = 1,150) was used for prevalence of AFHS. Group 3 (n = 1,213) had PET/CT and MRI pelvis within a week of each other and was used to correlate metabolic and anatomic findings. Group 4 (n = 100) was used to generate the control group. Data were collected on demographics, common comorbidities, underlying cancer diagnosis and status, and hip symptoms. Prevalence of AFHS was 0.36 % (95 % CI 0.10-0.91 %). None progressed to malignancy or was associated with cancer status. The majority (71 %) were on the left, and 6 % were bilateral. Mean SUV{sub max} of the AFHS was 4.8 (range, 2.7-7.8). Male patients were more likely to have the AFHS (OR = 8.69, 95 % CI 1.88-40.13). There was no difference with respect to other collected data, including hip symptoms. Average minimum duration of AFHS was 346 days (range, 50-1,010 days). Readers did not detect corresponding hip abnormalities on MRIs. AFHS is a benign finding that may be caused by subclinical ligamentum teres injury, focal synovitis, or degeneration of acetabular fossa fat. Despite uncertainty regarding its etiology, recognition of AFHS as a benign finding can prevent morbidity associated with unnecessary biopsy or initiation of therapy. (orig.)

  16. Spatial and Temporal Hot Spots of Aedes albopictus Abundance inside and outside a South European Metropolitan Area.

    Directory of Open Access Journals (Sweden)

    Mattia Manica

    2016-06-01

    Full Text Available Aedes albopictus is a tropical invasive species which in the last decades spread worldwide, also colonizing temperate regions of Europe and US, where it has become a public health concern due to its ability to transmit exotic arboviruses, as well as severe nuisance problems due to its aggressive daytime outdoor biting behaviour. While several studies have been carried out in order to predict the potential limits of the species expansions based on eco-climatic parameters, few studies have so far focused on the specific effects of these variables in shaping its micro-geographic abundance and dynamics. The present study investigated eco-climatic factors affecting Ae. albopictus abundance and dynamics in metropolitan and sub-urban/rural sites in Rome (Italy, which was colonized in 1997 and is nowadays one of the most infested metropolitan areas in Southern Europe. To this aim, longitudinal adult monitoring was carried out along a 70 km-transect across and beyond the most urbanized and densely populated metropolitan area. Two fine scale spatiotemporal datasets (one with reference to a 20m circular buffer around sticky traps used to collect mosquitoes and the second to a 300m circular buffer within each sampling site were exploited to analyze the effect of climatic and socio-environmental variables on Ae. albopictus abundance and dynamics along the transect. Results showed an association between highly anthropized habitats and high adult abundance both in metropolitan and sub-urban/rural areas, with "small green islands" corresponding to hot spots of abundance in the metropolitan areas only, and a bimodal seasonal dynamics with a second peak of abundance in autumn, due to heavy rains occurring in the preceding weeks in association with permissive temperatures. The results provide useful indications to prioritize public mosquito control measures in temperate urban areas where nuisance, human-mosquito contact and risk of local arbovirus transmission are

  17. Spatial and Temporal Hot Spots of Aedes albopictus Abundance inside and outside a South European Metropolitan Area.

    Science.gov (United States)

    Manica, Mattia; Filipponi, Federico; D'Alessandro, Antonello; Screti, Alessia; Neteler, Markus; Rosà, Roberto; Solimini, Angelo; Della Torre, Alessandra; Caputo, Beniamino

    2016-06-01

    Aedes albopictus is a tropical invasive species which in the last decades spread worldwide, also colonizing temperate regions of Europe and US, where it has become a public health concern due to its ability to transmit exotic arboviruses, as well as severe nuisance problems due to its aggressive daytime outdoor biting behaviour. While several studies have been carried out in order to predict the potential limits of the species expansions based on eco-climatic parameters, few studies have so far focused on the specific effects of these variables in shaping its micro-geographic abundance and dynamics. The present study investigated eco-climatic factors affecting Ae. albopictus abundance and dynamics in metropolitan and sub-urban/rural sites in Rome (Italy), which was colonized in 1997 and is nowadays one of the most infested metropolitan areas in Southern Europe. To this aim, longitudinal adult monitoring was carried out along a 70 km-transect across and beyond the most urbanized and densely populated metropolitan area. Two fine scale spatiotemporal datasets (one with reference to a 20m circular buffer around sticky traps used to collect mosquitoes and the second to a 300m circular buffer within each sampling site) were exploited to analyze the effect of climatic and socio-environmental variables on Ae. albopictus abundance and dynamics along the transect. Results showed an association between highly anthropized habitats and high adult abundance both in metropolitan and sub-urban/rural areas, with "small green islands" corresponding to hot spots of abundance in the metropolitan areas only, and a bimodal seasonal dynamics with a second peak of abundance in autumn, due to heavy rains occurring in the preceding weeks in association with permissive temperatures. The results provide useful indications to prioritize public mosquito control measures in temperate urban areas where nuisance, human-mosquito contact and risk of local arbovirus transmission are likely higher

  18. Fluorescence enhancement using Fano-resonant a plasmonic nanostructure with selective functionalization of molecules at the electromagnetic hot spot (Presentation Recording)

    Science.gov (United States)

    Wang, Xiaolong; Martin, Olivier J. F.

    2015-09-01

    In recent years, one has paid significant attention to plasmonic nanostructures due to their potential for practical applications. Especially, in most plasmonic nanostructures, the local density of optical states is strongly enhanced and confined in the nanogap region - like for example in plasmonic antennas - which results in the so-called electromagnetic hot spots. In this work, we use 4-nanorod structures made with silver to generate and tune Fano resonances exhibiting an asymmetric and narrow lineshape. In such a system, a strongly enhanced electromagnetic field is created in the nanogap when the two antenna modes undergo destructive interference, i.e. at the Fano resonance. The local near field is thus strongly enhanced since most of the energy is not radiated into the far field at that wavelength. We will show that using a 4-nanorod structure in silver, we can easily tune the Fano resonance through the fluorescence spectrum of the molecule under study, thus exploring the different resonance conditions between the molecule absorption/emission bands and the plasmonic nanostructure; both the excitation and emission rates of the molecule can be enhanced when it is placed within the hot spot. To this end, we have developed a double electron beam lithography process to fabricate the plasmonic nanostructures and then selectively immobilize the molecule in the hot spot, in order to investigate the fluorescence enhancement under well-controlled conditions. The fluorescence enhancement is demonstrated by measuring the fluorescence lifetime and the fluorescence count rate. The experimental results are supported by theoretical modelling and numerical calculations with the Green's tensor method.

  19. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    OpenAIRE

    de Carvalho, Vanuildo S.; Freire, Hermann

    2013-01-01

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\\delta}$ by Chatterjee \\emph{et al.} [Nature Physics \\textbf{6}, 99 (2010)], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model consisting of eight points located near the "hot spots" on the Fermi surface which are directly connected by spin density wave ordering wave vector. We derive RG equations up to two-loop order ...

  20. Relevance of hot spots in the evolution and transmission of Tn1546 in glycopeptide-resistant Enterococcus faecium (GREF) from broiler origin

    DEFF Research Database (Denmark)

    Migura, Lourdes Garcia; Hasman, Henrik; Svendsen, Christina Aaby;

    2008-01-01

    -resistant Enterococcus faecium isolated from broiler farms. Methods: Total DNA was digested, ligated and amplified using primers from inside Tn1546. The resulting amplicons were purified and sequenced. Two new primers were designed based on obtained sequences. Results: Two main insertion points have been repeatedly......) was duplicated as previously described, indicating transposition at the target site. Furthermore, this 'hot spot' was also detected in isolates from Norway (2/8) and Denmark (17/20). The second insertion point detected in 45 isolates from the UK revealed integration into an Inc18-like plasmid, most likely...

  1. Bear Creek Valley Floodplain hot spot removal early action characterization field data summary report, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This report summarizes the field and laboratory efforts as a result of the Bear Creek Floodplain Hot Spot Removal Project Early Action. The purpose of this project was to collect data necessary to assess contaminant levels in the Bear Creek Valley Floodplain and evaluate the risk posed by the sites. This report provides information on the background of the site, characterization of site and field activities, results of field and laboratory data collected, extent and distribution of contamination, and an assessment of the future risk posed by the site.

  2. Study on unified fatigue strength assessment method for welded structure. Hot spot stress evaluating method for various combinations of plate thickness and weld leg length; Yosetsu kozo no toitsutekina hiro kyodo hyokaho ni kansuru kenkyu. Itaatsu to yosetsu ashinaga no kumiawase ni taisuru hot spot oryoku sanshutsu ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nihei, K.; Inamura, F.; Koe, S. [Kawasaki Heavy Industries, Ltd., Kobe (Japan)

    1996-12-31

    There has been tried to apply unified assessment method using hot spot stress, which is effective to evaluate fatigue strength of fillet welded structures for ships and marine structures. This method can be applied to complicated structures and is independent of welding processes. In this study, first, stress analysis has been conducted for two-dimensional fillet welded joint models with various combinations of plate thickness and weld leg length of general fillet structures by means of boundary element method. Then, critical position, which is not affected by local stress concentration due to bead, was determined from the detailed stress distribution in the vicinity of weld toe. As a result, a general equation has been proposed to estimate the hot spot stress by one-point representative method. Second, the fatigue tests of typical fillet welded joints have been conducted by applying this method. Consequently, it was demonstrated that the unified fatigue strength can be evaluated by the S-N data based on hot spot stress range determined from the proposed equation, independent of structural stress concentration. 22 refs., 14 figs.

  3. Allosteric modulation of caspases.

    Science.gov (United States)

    Häcker, Hans-Georg; Sisay, Mihiret Tekeste; Gütschow, Michael

    2011-11-01

    Caspases are proteolytic enzymes mainly involved in the induction and execution phases of apoptosis. This type of programmed cell death is an essential regulatory process required to maintain the integrity and homeostasis of multicellular organisms. Inappropriate apoptosis is attributed a key role in many human diseases, including neurodegenerative disorders, ischemic damage, autoimmune diseases and cancer. Allosteric modulation of the function of a protein occurs when the regulatory trigger, such as the binding of a small effector or inhibitor molecule, takes place some distance from the protein's active site. In recent years, several caspases have been identified that possess allosteric sites and binding of small molecule to these sites resulted in the modulation of enzyme activities. Regulation of caspase activity by small molecule allosteric modulators is believed to be of great therapeutic importance. In this review we give brief highlights on recent developments in identifying and characterizing natural and synthetic allosteric inhibitors as well as activators of caspases and discuss their potential in drug discovery and protein engineering. PMID:21807025

  4. Determination of site selectivity of different carcinogens for preferential mutational hot spots in oligonucleotide fragments by ion-pair reversed-phase nano liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Sharma, Vaneet K; Xiong, Wennan; Glick, James; Vouros, Paul

    2014-01-01

    Ion-pair reversed-phase nano liquid chromatography coupled with nanospray ion trap mass spectrometry was used to investigate site selectivity of the known carcinogens N-acetoxy-2-acetylaminofluorene, N-hydroxy-4-aminobiphenyl and (+/-)-anti-benzo[a]pyrene diol epoxide with the synthetic double-strand 14-mer long oligonucleotide fragment of the p53 gene containing two mutational hot-spot codons (5'-P-ACC155 CGC156 GTC157 CGC158 GC/5'-GCG CGG ACG CGG GT). The investigation was performed using a monolithic polystyrene divinylbenzene capillary column and triethylammonium bicarbonate as an ion-pair reagent. The exact location of the carcinogen on the modified oligonucleotide backbone was determined using characteristic collision-induced dissociation fragmentation patterns obtained under negative-ion mode ionization. In all these cases, the adducted, isomeric oligonucleotides formed were chromatographically resolved and structural identification was performed without any prior deoxyribonucleic acid cleavage or hydrolysis. The knowledge of the site specificity of a carcinogen, especially at purported mutational hot spots, is of paramount importance (1) in establishing the identity of biomarkers for an early risk assessment of the formed DNA adducts, (2) developing repair mechanisms for the formed carcinogen adducted DNA, and (3) understanding the nature of the covalent bond formed and mapping the frequency of the adduction process. PMID:24881456

  5. Presaging critical residues in protein interfaces-web server (PCRPi-W: a web server to chart hot spots in protein interfaces.

    Directory of Open Access Journals (Sweden)

    Joan Segura Mora

    Full Text Available BACKGROUND: It is well established that only a portion of residues that mediate protein-protein interactions (PPIs, the so-called hot spot, contributes the most to the total binding energy, and thus its identification is an important and relevant question that has clear applications in drug discovery and protein design. The experimental identification of hot spots is however a lengthy and costly process, and thus there is an interest in computational tools that can complement and guide experimental efforts. PRINCIPAL FINDINGS: Here, we present Presaging Critical Residues in Protein interfaces-Web server (http://www.bioinsilico.org/PCRPi, a web server that implements a recently described and highly accurate computational tool designed to predict critical residues in protein interfaces: PCRPi. PRCPi depends on the integration of structural, energetic, and evolutionary-based measures by using Bayesian Networks (BNs. CONCLUSIONS: PCRPi-W has been designed to provide an easy and convenient access to the broad scientific community. Predictions are readily available for download or presented in a web page that includes among other information links to relevant files, sequence information, and a Jmol applet to visualize and analyze the predictions in the context of the protein structure.

  6. Using penumbral imaging to measure micrometer size plasma hot spots in Gbar equation of state experiments on the National Ignition Facility

    Science.gov (United States)

    Bachmann, B.; Kritcher, A. L.; Benedetti, L. R.; Falcone, R. W.; Glenn, S.; Hawreliak, J.; Izumi, N.; Kraus, D.; Landen, O. L.; Le Pape, S.; Ma, T.; Pérez, F.; Swift, D.; Döppner, T.

    2014-11-01

    We have developed an experimental platform for absolute equation of state measurements up to Gbar pressures on the National Ignition Facility (NIF) within the Fundamental Science Program. We use a symmetry-tuned hohlraum drive to launch a spherical shock wave into a solid CH sphere. Streaked radiography is the primary diagnostic to measure the density change at the shock front as the pressure increases towards smaller radii. At shock stagnation in the center of the capsule, we observe a short and bright x-ray self emission from high density (˜50 g/cm3) plasma at ˜1 keV. Here, we present results obtained with penumbral imaging which has been carried out to characterize the size of the hot spot emission. This allows extending existing NIF diagnostic capabilities for spatial resolution (currently ˜10 μm) at higher sensitivity. At peak emission we find the hot spot radius to be as small as 5.8 +/- 1 μm, corresponding to a convergence ratio of 200.

  7. The research of internet public opinion hot spot mining%网络舆情热点挖掘算法研究与实现

    Institute of Scientific and Technical Information of China (English)

    黄敏

    2012-01-01

    随着网络信息交互及传播的迅速与便捷,有效地对不断涌现的海量互联网信息进行采集并发现网络热点舆情具有十分重要的意义.研究网络舆情的表示及特征,提出采用网络化方法思想,结合Hits算法和PageRank算法进行舆情热点挖掘,并在此基础上设计了网络舆情热点挖掘系统.%With the speedy interaction and spread of the network information, it has great significance to collect emerging massive internet information and discover hot spots of network public opinion. This paper studied the characteristics of network public opinion and designed hot spot mining system on the basis of combination of Hits and PageRank algorithms.

  8. Validation of the DIFFAL, HPAC and HotSpot Dispersion Models Using the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials Witness Plate Deposition Dataset.

    Science.gov (United States)

    Purves, Murray; Parkes, David

    2016-05-01

    Three atmospheric dispersion models--DIFFAL, HPAC, and HotSpot--of differing complexities have been validated against the witness plate deposition dataset taken during the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials. The small-scale nature of these trials in comparison to many other historical radiological dispersion trials provides a unique opportunity to evaluate the near-field performance of the models considered. This paper performs validation of these models using two graphical methods of comparison: deposition contour plots and hotline profile graphs. All of the models tested are assessed to perform well, especially considering that previous model developments and validations have been focused on larger-scale scenarios. Of the models, HPAC generally produced the most accurate results, especially at locations within ∼100 m of GZ. Features present within the observed data, such as hot spots, were not well modeled by any of the codes considered. Additionally, it was found that an increase in the complexity of the meteorological data input to the models did not necessarily lead to an improvement in model accuracy; this is potentially due to the small-scale nature of the trials.

  9. Using penumbral imaging to measure micrometer size plasma hot spots in Gbar equation of state experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, B., E-mail: bachmann2@llnl.gov; Kritcher, A. L.; Benedetti, L. R.; Glenn, S.; Hawreliak, J.; Izumi, N.; Landen, O. L.; Le Pape, S.; Ma, T.; Pérez, F.; Swift, D.; Döppner, T. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Falcone, R. W. [Department of Physics, University of California, Berkeley, California 94720 (United States); Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Kraus, D. [Department of Physics, University of California, Berkeley, California 94720 (United States)

    2014-11-15

    We have developed an experimental platform for absolute equation of state measurements up to Gbar pressures on the National Ignition Facility (NIF) within the Fundamental Science Program. We use a symmetry-tuned hohlraum drive to launch a spherical shock wave into a solid CH sphere. Streaked radiography is the primary diagnostic to measure the density change at the shock front as the pressure increases towards smaller radii. At shock stagnation in the center of the capsule, we observe a short and bright x-ray self emission from high density (∼50 g/cm{sup 3}) plasma at ∼1 keV. Here, we present results obtained with penumbral imaging which has been carried out to characterize the size of the hot spot emission. This allows extending existing NIF diagnostic capabilities for spatial resolution (currently ∼10 μm) at higher sensitivity. At peak emission we find the hot spot radius to be as small as 5.8 +/− 1 μm, corresponding to a convergence ratio of 200.

  10. Controlling allosteric networks in proteins

    Science.gov (United States)

    Dokholyan, Nikolay

    2013-03-01

    We present a novel methodology based on graph theory and discrete molecular dynamics simulations for delineating allosteric pathways in proteins. We use this methodology to uncover the structural mechanisms responsible for coupling of distal sites on proteins and utilize it for allosteric modulation of proteins. We will present examples where inference of allosteric networks and its rewiring allows us to ``rescue'' cystic fibrosis transmembrane conductance regulator (CFTR), a protein associated with fatal genetic disease cystic fibrosis. We also use our methodology to control protein function allosterically. We design a novel protein domain that can be inserted into identified allosteric site of target protein. Using a drug that binds to our domain, we alter the function of the target protein. We successfully tested this methodology in vitro, in living cells and in zebrafish. We further demonstrate transferability of our allosteric modulation methodology to other systems and extend it to become ligh-activatable.

  11. 75 FR 29537 - Draft Transportation Conformity Guidance for Quantitative Hot-spot Analyses in PM2.5

    Science.gov (United States)

    2010-05-26

    .... In its March 10, 2006 final rule (71 FR 12468), EPA stated that quantitative PM 2.5 and PM 10 hot... (58 FR 62188) and has subsequently published several amendments. II. Background on the Draft Guidance... its March 2006 final rule (71 FR 12502), this draft guidance was developed in coordination with...

  12. Doubling the efficiency of third harmonic generation by positioning ITO nanocrystals into the hot-spot of plasmonic gap-antennas.

    Science.gov (United States)

    Metzger, Bernd; Hentschel, Mario; Schumacher, Thorsten; Lippitz, Markus; Ye, Xingchen; Murray, Christopher B; Knabe, Bastian; Buse, Karsten; Giessen, Harald

    2014-05-14

    We incorporate dielectric indium tin oxide nanocrystals into the hot-spot of gold nanogap-antennas and perform third harmonic spectroscopy on these hybrid nanostructure arrays. The combined system shows a 2-fold increase of the radiated third harmonic intensity when compared to bare gold antennas. In order to identify the origin of the enhanced nonlinear response we perform finite element simulations of the nanostructures, which are in excellent agreement with our measurements. We find that the third harmonic signal enhancement is mainly related to changes in the linear optical properties of the plasmonic antenna resonances when the ITO nanocrystals are incorporated. Furthermore, the dominant source of the third harmonic is found to be located in the gold volume of the plasmonic antennas.

  13. A hot-spot-active magnetic graphene oxide substrate for microRNA detection based on cascaded chemiluminescence resonance energy transfer

    Science.gov (United States)

    Bi, Sai; Chen, Min; Jia, Xiaoqiang; Dong, Ying

    2015-02-01

    Herein, a cascaded chemiluminescence resonance energy transfer (C-CRET) process was demonstrated from horseradish peroxidase (HRP)-mimicking DNAzyme-catalyzed luminol-H2O2 to fluorescein and further to graphene oxide (GO) when HRP-mimicking DNAzyme/fluorescein was in close proximity to the GO surface. The proposed C-CRET system was successfully implemented to construct three modes of C-CRET hot-spot-active substrates (modes I, II and III) by covalently immobilizing HRP-mimicking DNAzyme/fluorescein-labeled hairpin DNAs (hot-spot-generation probes) on magnetic GO (MGO), resulting in a signal ``off'' state due to the quenching of the luminol/H2O2/HRP-mimicking DNAzyme/fluorescein CRET system by GO. Upon the introduction of microRNA-122 (miRNA-122), the targets (mode I) or the new triggers that were generated through a strand displacement reaction (SDR) initiated by miRNA-122 (modes II and III) hybridized with the loop domains of hairpin probes on MGO to form double-stranded (modes I and II) or triplex-stem structures (mode III), causing an ``open'' configuration of the hairpin probe and a CRET signal ``on'' state, thus achieving sensitive and selective detection of miRNA-122. More importantly, the substrate exhibited excellent controllability, reversibility and reproducibility through SDR and magnetic separation (modes II and III), especially sequence-independence for hairpin probes in mode III, holding great potential for the development of a versatile platform for optical biosensing.Herein, a cascaded chemiluminescence resonance energy transfer (C-CRET) process was demonstrated from horseradish peroxidase (HRP)-mimicking DNAzyme-catalyzed luminol-H2O2 to fluorescein and further to graphene oxide (GO) when HRP-mimicking DNAzyme/fluorescein was in close proximity to the GO surface. The proposed C-CRET system was successfully implemented to construct three modes of C-CRET hot-spot-active substrates (modes I, II and III) by covalently immobilizing HRP-mimicking DNAzyme

  14. Analysis of Reactive Hot Spot for Thermite under Shock Waves%铝热剂反应性冲击热点分析

    Institute of Scientific and Technical Information of China (English)

    王新征; 张松林; 张庆明; 秦志桂; 陈旻; 李文杰

    2012-01-01

    采用激光粒度扫描仪测量了二元混合物铝热剂(Al+Fe2O3)原料的粒径分布,在电子显微镜下观察了铝颗粒、氧化铁颗粒的颗粒形状及两者按照化学配比混合后的颗粒接触状态。综合粒径分布和反应体系的化学配比关系,得到两种反应物的特征粒径和混合物的颗粒布局。根据特征粒径和颗粒布局,建立了该反应体系的等效细观模型,该细观模型能够保证得到与实际颗粒体系相一致的具有统计意义的孔穴结构。采用无网格粒子方法,数值模拟了铝热剂体系在不同冲击速度作用下,基本氧化铁颗粒排列形成的热点特征。研究表明,氧化铁三颗粒紧密排列的模式为形成单独热点的最基本排列,在平面冲击作用下,二元不同粒径的含能材料混合物形成热点的尺寸由初始孔穴尺寸确定,而热点温度受冲击速度影响较大。采用轻气炮对不同密度和配比的铝热剂进行了冲击点火实验,并将测量和数值计算结果进行了对比分析,结果表明,两者的定性结论吻合较好。%Using laser scaners to measure the size of binary mixture of energetic materials thermite (Al+Fe2O3 ) and get the particle size distribution,the particle shape of aluminum powder,iron oxide and the contact status of the mixtures meeting the standard chemical proportion are observed under the electron microscope. Combined the raw material particle size distribution and the mass ratio of chemical reaction,the particle characteristic size (equivalent volume radius) and arrangement of aluminum and iron oxide particle were obtained. Based on the above conditions, the mesoscopic model for the thermite mixtures was established. The mesoscopic model can be guaranteed to get the statistical cavities struc- ture consistent with that of the actual granular system. The features of "hot spot" for the thermite by impact were studied with the Smoothed Particle

  15. An outdoor investigation of the absorption degradation of single-junction amorphous silicon photovoltaic module due to localized heat/hot spot formation

    Indian Academy of Sciences (India)

    Osayemwenre Gilbert O; Meyer Edson L; Mamphweli Sampson

    2016-04-01

    This paper investigates the absorbance degradation of single-junction amorphous silicon (a-Si:H) photovoltaic (PV) module, due to the presence of localized heat. The decrease in optical density is a huge challenge due to the long-term degradation of PV modules. The reduction in solar cell optical density causes a decline in its conversion efficiency. This decreases the photogenerating current, hence reduces the effective efficiency of the PV device. An infrared thermography was used for mapping the module temperature profile. Fourier transform infrared spectroscopy (FTIR) was used for the absorption characterization. The rationale behind the outdoor deployment was to deduce a practical effect of hot spot formation on the module’s absorption ability.The results show a direct correlation between localized heat and the absorption degradation.

  16. Characteristics of hot spots of melon fly, Bactrocera (Dacus) cucurbitae Coquillett (Diptera: Tephritidae) in sterile fly release areas on Okinawa island [Japan

    International Nuclear Information System (INIS)

    The spatio-temporal dynamics of populations of the melon fly, Bactrocera (Dacus) cucurbitae COQUILLETT, in the southern part of Okinawa Island where an eradication program using sterile flies has been conducted, were analyzed in relation to the seasonal succession and abundance of wild and cultivated host fruits. The study areas were classified into four major zones according to the seasonal abundance of flies caught by cue-lure traps and the availability of host fruits including Diplocyclos palmatus, Melothria liukiuensis and Momordica charantia var. pevel. Zone-I is characterized by the continuous presence of host fruits and a relatively-high population density of the melon fly indicated by the cue-lure trap catch of more than 1, 000 flies per 1, 000 traps per day throughout the year. Zone-II has a characteristic decline in both number of host fruits and fly density during the fall-winter period with an annual average of less than 1, 000 flies per 1, 000 traps per day. Zone-III includes areas where host fruits and flies (about 1 fly/trap/day) were relatively abundant only during the winter-spring period. Zone-IV is characterized by constantly low availability of host fruits and low fly density throughout the year. Hot spots, which are defined as areas where the ratio of sterile to wild flies hardly increases despite frequent and intensive release of sterile flies, were found in the Zone-I areas. Therefore, the continuous presence and abundance of host fruits appears to hot spots. For effective control of this species, it is essential to locate such areas and release sterile flies

  17. A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping.

    Directory of Open Access Journals (Sweden)

    Gemma L Walmsley

    Full Text Available BACKGROUND: Duchenne muscular dystrophy (DMD, which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion "hot spot" is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD "hot spot". METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD. The dogs harbour a missense mutation in the 5' donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression. CONCLUSIONS/SIGNIFICANCE: Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD.

  18. Identification of 'carbon hot-spots' and quantification of GHG intensities in the biodiesel supply chain using hybrid LCA and structural path analysis.

    Science.gov (United States)

    Acquaye, Adolf A; Wiedmann, Thomas; Feng, Kuishang; Crawford, Robert H; Barrett, John; Kuylenstierna, Johan; Duffy, Aidan P; Koh, S C Lenny; McQueen-Mason, Simon

    2011-03-15

    It is expected that biodiesel production in the EU will remain the dominant contributor as part of a 10% minimum binding target for biofuel in transportation fuel by 2020 within the 20% renewable energy target in the overall EU energy mix. Life cycle assessments (LCA) of biodiesel to evaluate its environmental impacts have, however, remained questionable, mainly because of the adoption of a traditional process analysis approach resulting in system boundary truncation and because of issues regarding the impacts of land use change and N(2)O emissions from fertilizer application. In this study, a hybrid LCA methodology is used to evaluate the life cycle CO(2) equivalent emissions of rape methyl ester (RME) biodiesel. The methodology uses input-output analysis to estimate upstream indirect emissions in order to complement traditional process LCA in a hybrid framework. It was estimated that traditional LCA accounted for 2.7 kg CO(2)-eq per kg of RME or 36.6% of total life cycle emissions of the RME supply chin. Further to the inclusion of upstream indirect impacts in the LCA system (which accounted for 23% of the total life cycle emissions), emissions due to direct land use change (6%) and indirect land use change (16.5%) and N(2)O emissions from fertilizer applications (17.9%) were also calculated. Structural path analysis is used to decompose upstream indirect emissions paths of the biodiesel supply chain in order to identify, quantify, and rank high carbon emissions paths or 'hot-spots' in the biodiesel supply chain. It was shown, for instance, that inputs from the 'Other Chemical Products' sector (identified as phosphoric acid, H(3)PO(4)) into the biodiesel production process represented the highest carbon emission path (or hot-spot) with 5.35% of total upstream indirect emissions of the RME biodiesel supply chain. PMID:21319814

  19. Allosteric Mechanisms in Chaperonin Machines.

    Science.gov (United States)

    Gruber, Ranit; Horovitz, Amnon

    2016-06-01

    Chaperonins are nanomachines that facilitate protein folding by undergoing energy (ATP)-dependent movements that are coordinated in time and space owing to complex allosteric regulation. They consist of two back-to-back stacked oligomeric rings with a cavity at each end where protein substrate folding can take place. Here, we focus on the GroEL/GroES chaperonin system from Escherichia coli and, to a lesser extent, on the more poorly characterized eukaryotic chaperonin CCT/TRiC. We describe their various functional (allosteric) states and how they are affected by substrates and allosteric effectors that include ATP, ADP, nonfolded protein substrates, potassium ions, and GroES (in the case of GroEL). We also discuss the pathways of intra- and inter-ring allosteric communication by which they interconvert and the coupling between allosteric transitions and protein folding reactions. PMID:26726755

  20. Evaluation of Caspofungin Susceptibility Testing by the New Vitek 2 AST-YS06 Yeast Card Using a Unique Collection of FKS Wild-Type and Hot Spot Mutant Isolates, Including the Five Most Common Candida Species

    DEFF Research Database (Denmark)

    Astvad, Karen M; Perlin, David S; Johansen, Helle K;

    2013-01-01

    susceptibility card to correctly identify the fks mutants from wt isolates and compared the performance to those of the CLSI and EUCAST reference methods. A collection of 98 Candida isolates, including 31 fks hot spot mutants, were included. Performance was evaluated using the FKS genotype as the "gold standard...

  1. Internet Public Opinion Hot Spot Mining Base on Complex Network Theory%基于复杂网络方法的舆情热点挖掘

    Institute of Scientific and Technical Information of China (English)

    黄敏; 胡学钢

    2011-01-01

    This paper focused on the Internet public opinion hot spot mining based on the complex network theory and methods. Internet public opinion analysis techniques can be divided into content-based analytical methods and analyses based on data mining methods. Both are traditional technology and have no relation with the network. This paper gave the idea of public opinion analyses and proposed a network-based approach to resolve network problems. The public opinion web pages could be represented as nodes of complex networks and the sides were links of those pages. The public opinion network meets the complex network characteristics. Based on Hits algorithm and PageRank algorithm, we can find out the most popular public opinions in the network, which showed a hot public opinion. With a data set from Wikipedia, experimental results show that both methods can identify hot spots of public opinion networks. Because PageRank method focuses on the impact of link nodes and Hits algorithm focus on the core degree of the nodes, the mining results have some difference. We can combine the mining results of the two methods according to the field characteristics to get the Internet public opinion hot spots.%研究使用复杂网络理论和算法的网络舆情热点提取.网络舆情分析技术可以分为基于内容的分析方法和基于数据挖掘的分析方法,二者均是采用传统技术处理网络舆情,并未结合网络特性.针对上述问题,开拓了舆情分析的思路,提出采用网络化方法处理网络问题的思想,将舆情网络的页面视为节点,链接关系作为边,构建符合复杂网络特征的舆情传播网络.使用PageRank算法和Hits算法,可以挖掘出舆情网络中的重要节点,进而发现舆情热点.以维基百科数据为仿真数据集,采用新提出的方法,可以挖掘相关领域的热点条目.仿真结果表明,两种方法均可以完成网络舆情热点的发掘工作,从复杂网络的角度处理网络舆情

  2. A new assessment of combined geothermal electric generation and desalination in western Saudi Arabia: targeted hot spot development

    KAUST Repository

    Missimer, Thomas M.

    2014-07-17

    High heat flow associated with the tectonic spreading of the Red Sea make western Saudi Arabia a region with high potential for geothermal energy development. The hydraulic properties of the Precambrian-age rocks occurring in this region are not conducive to direct production of hot water for heat exchange, which will necessitate use of the hot dry rock (HDR) heat harvesting method. This would require the construction of coupled deep wells; one for water injection and the other for steam recovery. There are some technological challenges in the design, construction, and operation of HDR geothermal energy systems. Careful geotechnical evaluation of the heat reservoir must be conducted to ascertain the geothermal gradient at the chosen site to allow pre-design modeling of the system for assessment of operational heat flow maintenance. Also, naturally occurring fractures or faults must be carefully evaluated to make an assessment of the potential for induced seismicity. It is anticipated that the flow heat exchange capacity of the system will require enhancement by the use of horizontal drilling and hydraulic fracturing in the injection well with the production well drilled into the fracture zone to maximum water recovery efficiency and reduce operating pressure. The heated water must be maintained under pressure and flashed to steam at surface to produce to the most effective energy recovery. Most past evaluations of geothermal energy development in this region have been focused on the potential for solely electricity generation, but direct use of produced steam could be coupled with thermally driven desalination technologies such as multi-effect distillation, adsorption desalination, and/or membrane distillation to provide a continuous source of heat to allow very efficient operation of the plants. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  3. Hydrothermal vents near a mantle hot spot: the Lucky Strike vent field at 37°N on the Mid-Atlantic Ridge

    Science.gov (United States)

    Langmuir, C.; Humphris, S.; Fornari, D.; Van Dover, C.; Von Damm, K.; Tivey, M. K.; Colodner, D.; Charlou, J.-L.; Desonie, D.; Wilson, C.; Fouquet, Y.; Klinkhammer, G.; Bougault, H.

    1997-04-01

    The Lucky Strike hydrothermal field occurs in the summit basin of a large seamount that forms the shallow center of a 65 km long ridge segment near 37°N on the Mid-Atlantic Ridge. The depth and chemistry of the ridge segment are influenced by the Azores hot spot, and this hydrothermal field is the first Atlantic site found on crust that is dominated by a hot spot signature. Multiple hydrothermal vents occur over an area of at least 300 m by 700 m. Vent morphologies range from flanges and chimneys with temperatures of 200-212°C, to black smoker chimneys with temperatures up to 333°C. Cooler fluids from northern vents have higher chlorinities and lower gas volumes, while hotter, southern fluids have chlorinities 20% below seawater with higher gas volumes, suggesting phase separation has influenced their compositions. All gas volumes in fluids are higher than those at TAG and Snake Pit hydrothermal fields. Black smokers exhibit their typical mineralogy, except that barite is a major mineral, particularly at lower-temperature sites, which contrasts with previously investigated Atlantic sites. The fluid chemistry, distribution of the relict sulfide deposits on the seamount summit in the areas investigated using DSV Alvin, and contact relationships between active vent sites and surrounding basaltic and sulfide substrate suggest that the hydrothermal system has a long history and may have recently been rejuvenated. Fauna at the Lucky Strike vent sites are dominated by a new species of mussel, and include the first reported sea urchins. The Lucky Strike biological community differs considerably from other vent fauna at the species level and appears to be a new biogeographic province. The Lucky Strike field helps to constrain how variations in the basaltic substrate influence the composition of hydrothermal fluids and solids, because basalt compositions at Lucky Strike are 10-30 times enriched in incompatible elements compared to other Atlantic hydrothermal sites such as

  4. 国内网络舆情研究热点与趋势分析%Domestic Internet Public Opinion Research Hot Spot and Trend

    Institute of Scientific and Technical Information of China (English)

    卢卉; 黄建忠

    2011-01-01

    目的 了解国内网络舆情热点,提高舆情监测能力,为政府及相关部门决策提供服务.方法 通过下载CNKI收录的网络舆情论文(2005 - 2010年),借助于统计软件与科学计量方法对近6年来我国网络舆情的研究状况进行分析.结果 研究的热点问题为文本挖掘、引导、高校、突发事件、模型、舆情分析、预警、指标体系等;舆情研究已进入了发展阶段,形成了一批高产作者和出名的研究机构,部分阶段性研究成果已在网络舆情监测系统中得到应用.结论 舆情研究已进入了发展阶段,舆情监测工作应从实际需求出发,实时研究舆情发展趋势.%Objective To provide services for the decision meking of government and relevant departments by understanding the hot spot of the domestic internet public opinion and improving the monitoring capacity of public opinion. Methods Downloaded the domestic internet public opinion papers in CNKI (2005 -2010), with the situation of domestic internet public opinion in the past six years was analyzed by means of statistical software and scientific measurement methods. Results The research hot spot topics were the text mining, guide, college, emergency, models, public opinion analysis, early warning, indicator system and, etc. Public opinion research has entered the developing stage, with a group of high production authors and famous research institutions has formed. Part of initial findings of public opinion research has been applied in network monitoring system. Conclusion Public opinion research has entered the developing stage. Public opinion mornitoring should based on the actual demand to conduct real - time study of the developing trend.

  5. Depth to Curie temperature or bottom of the magnetic sources in the volcanic zone of la Réunion hot spot

    Science.gov (United States)

    Gailler, Lydie-Sarah; Lénat, Jean-François; Blakely, Richard J.

    2016-09-01

    We present an innovative study to generalize Curie Point Depth (CPD) determinations at the scale of oceanic volcanic islands, an approach which has previously focused largely on continental areas. In order to determine the validity of this technique in oceanic environments, we first tested the approach on sets of sea-floor-spreading anomalies. Assuming that magnetic anomalies are concentrated within the oceanic crust and uppermost mantle, the Curie depth should deepen as oceanic lithosphere increases in age and thickness away from spreading centers. The calculated depths to the magnetic bottom are in agreement with this general pattern. On the basis of this test, we then applied the method to La Réunion Island and surrounding oceanic lithosphere. The calculated extent of magnetic sources lies at depths between 10 and 30 km and exhibits a complex topography, presumably caused by a combination of various magmatic and tectonic lithospheric structures. These calculations indicate that magnetic sources extend well below the crust-mantle interface at this location. To the first order, the bottom of the magnetic surface shallows beneath Réunion and Mauritius Islands due to the thermal effect of the hot spot, and deepens away from La Réunion edifice. On the scale of the Mascarene Basin, several discontinuities in the CPD correlate well with major fracture zones.

  6. Gene structure and hemocyanin isoform HtH2 from the mollusc Haliotis tuberculata indicate early and late intron hot spots.

    Science.gov (United States)

    Altenhein, Benjamin; Markl, Jürgen; Lieb, Bernhard

    2002-11-13

    We have cloned and sequenced cDNAs coding for the complete primary structure of HtH2, the second hemocyanin isoform of the marine gastropod Haliotis tuberculata. The deduced protein sequence comprises 3399 amino acids, corresponding to a molecular mass of 392 kDa. It shares only 66% of structural identity with the previously analysed first isoform HtH1, and according to a molecular clock, the two isoforms of Haliotis hemocyanin separated ca. 320 million years ago. By genomic polymerase chain reaction and 5' race, we have also sequenced the complete gene of HtH2 (18,598 bp), except of the 5' region in front of the secreted protein. It encompasses 15 exons and 14 introns and shows several microsatellite-rich regions. It mirrors the modular structure of the encoded hemocyanin subunit, with a linear arrangement of eight different functional units separated and bordered by seven phase 1 'linker introns'. In addition, within regions encoding three of the functional units, the HtH2 gene contains six 'internal introns'. Comparison to previously sequenced genes of Octopus dofleini hemocyanin and Haliotis hemocyanin isoform (HtH1) suggests Precambrian and Palaeocoic hot spot of intron gains, followed by 320 million years of absolute stasis. PMID:12490323

  7. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease

    Science.gov (United States)

    den-Haan, Helena; Pérez-Sánchez, Horacio; Del Prete, Rosita; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Andreotti, Giuseppina

    2016-01-01

    Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. PMID:27788225

  8. DnaK as Antibiotic Target: Hot Spot Residues Analysis for Differential Inhibition of the Bacterial Protein in Comparison with the Human HSP70.

    Directory of Open Access Journals (Sweden)

    Federica Chiappori

    Full Text Available DnaK, the bacterial homolog of human Hsp70, plays an important role in pathogens survival under stress conditions, like antibiotic therapies. This chaperone sequesters protein aggregates accumulated in bacteria during antibiotic treatment reducing the effect of the cure. Although different classes of DnaK inhibitors have been already designed, they present low specificity. DnaK is highly conserved in prokaryotes (identity 50-70%, which encourages the development of a unique inhibitor for many different bacterial strains. We used the DnaK of Acinetobacter baumannii as representative for our analysis, since it is one of the most important opportunistic human pathogens, exhibits a significant drug resistance and it has the ability to survive in hospital environments. The E.coli DnaK was also included in the analysis as reference structure due to its wide diffusion. Unfortunately, bacterial DnaK and human Hsp70 have an elevated sequence similarity. Therefore, we performed a differential analysis of DnaK and Hsp70 residues to identify hot spots in bacterial proteins that are not present in the human homolog, with the aim of characterizing the key pharmacological features necessary to design selective inhibitors for DnaK. Different conformations of DnaK and Hsp70 bound to known inhibitor-peptides for DnaK, and ineffective for Hsp70, have been analysed by molecular dynamics simulations to identify residues displaying stable and selective interactions with these peptides. Results achieved in this work show that there are some residues that can be used to build selective inhibitors for DnaK, which should be ineffective for the human Hsp70.

  9. High-resolution measurement of nitrous oxide in the Elbe estuary under hypoxia: Hot-spots of biological N2O production

    Science.gov (United States)

    Brase, Lisa; Lendt, Ralf; Sanders, Tina; Dähnke, Kirstin

    2016-04-01

    Nitrous oxide (N2O) is one of the most important greenhouse gases. Its global warming potential exceeds that of CO2 by a factor of ˜300. Estuaries, being sites of intense biological N-turnover, are one of the major natural sources of N2O emissions. On two ship cruises in April and June 2015, concentrations of N2O were measured in the surface water using equilibrator laser based on-line measurements. Based on these high-resolution N2O profiles along the Elbe estuary, N2O saturation and N2O-fluxes between surface water and air were calculated. Additionally, DIN concentrations and dual stable isotopes of nitrate (δ15N and δ18O) were analyzed. Concentration and water-to-air fluxes of N2O were highest in the Hamburg port region and dropped quickly further downstream. Highest water-to-air fluxes were up to 800μM/m2/d and 1600μM/m2/d in April and in June, respectively. Downstream of the port region, an N2O oversaturation of 150-200% was estimated over the entire estuary, with saturation approaching equilibrium (96-100%) only in the North Sea region. N2O production was much higher in June than in April 2015, likely coupled to lower oxygen saturation in the water column in June. Based on these measurements, the port of Hamburg region was identified as a hot-spot of N2O production. High N2O concentration and depleted values of nitrate isotopes suggest that nitrification is a significant source of N2O in the estuary, especially at low oxygen concentration. In the Elbe estuary, hypoxia obviously drastically increased the emissions of the greenhouse gas N2O.

  10. Structure of the lithosphere-asthenosphere system in the vicinity of the Tristan da Cunha hot spot as seen by surface waves

    Science.gov (United States)

    Geissler, Wolfram; Bonadio, Raffaele; Lebedev, Sergei; Jokat, Wilfried; Jegen, Marion; Baba, Kiyoshi; Sens-Schönfelder, Christoph

    2016-04-01

    According to classical plume theory, the Tristan da Cunha hotspot is thought to have played a major role in the rifting of the South Atlantic margins and the creation of the aseismic Walvis Ridge by impinging at the base of the continental lithosphere shortly before or during the breakup of the South Atlantic margins. However, Tristan da Cunha is enigmatic as it cannot be clearly identified as a hot spot but may also be classified as a more shallow type of anomaly that may actually have been caused by the opening of the South Atlantic. The equivocal character of Tristan da Cunha is largely due to a lack of geophysical and petrological data in this region. We therefore staged a multi-disciplinary geophysical study of the region by acquiring passive marine electromagnetic and seismic data, and bathymetric data within the framework of the SPP1375 South Atlantic Margin Processes and Links with onshore Evolution (SAMPLE) funded by the German Science foundation. The experiment included two ship expeditions onboard the German R/V MARIA S. MERIAN in 2012 and 2013. In our contribution we will present first results on the shear wave velocity structure of the lithosphere-asthenosphere system. We applied the classical two-station method; Rayleigh wave dispersion curves are determined by cross-correlation of seismograms from a pair of station. We measured interstation phase velocities of (earthquake-excited) fundamental-mode surface waves in a period range of 10 to 60 s. The selection of acceptable phase-velocity measurements in the frequency domain had to be done manually for each event. We present phase-velocity maps for the study area. Furthermore, we present 1D shear wave velocity models inverted from the highest-quality observations.

  11. Hunting for right and left parietal hot spots using single-pulse TMS: modulation of visuospatial perception during line bisection judgment in the healthy brain.

    Science.gov (United States)

    Salatino, Adriana; Poncini, Marisa; George, Mark S; Ricci, Raffaella

    2014-01-01

    A series of studies have consistently reproduced left neglect-like bias on line length estimation tasks in healthy participants by applying transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC), while no significant changes have been reported when stimulating the left PPC. However, a notable inter-individual variability in the right parietal site where TMS modulates visuospatial perception can be observed, and no general agreement exists on how to identify the optimal parietal site of stimulation. In the present study, we propose a new site-finding TMS protocol to easily identify the optimum parietal location, or "hot spot," where TMS may modulate visuospatial perception on a line length estimation task (the Landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset over nine different sites of a 3 cm × 3 cm grid, centred over right or left PPC (P4 and P3 according to the 10-20 EEG system, respectively) in eight healthy participants. Stimulation of right PPC induced a significant left neglect-like bias, when the coil was applied over the most posterior and dorso-posterior sites. Unexpectedly, TMS over left PPC also produced left neglect-like bias. However, in this case significant effects were found when targeting the most anterior and dorso-anterior portions of the grid. These results are discussed in relation to recent findings on neural networks underlying spatial cognition. The hunting protocol we propose might offer an economical and easy-to-use tool to functionally identify the optimal parietal site where TMS can modulate visuospatial perception, in healthy subjects and possibly in post-stroke patients undergoing repetitive transcranial magnetic stimulation treatment.

  12. 从文献分析看突发性耳聋的研究热点%Analysis the Hot Spots of Sudden Deafness by Researching Articles

    Institute of Scientific and Technical Information of China (English)

    向杰; 刘博

    2015-01-01

    Objective To better understand the hot spots and breakthrough on sudden deafness by searching and reading the papers in recent 5 years published in the PUBMED and the CNKI.Methods Use the Mesh term“Hearing Loss,Sudden”to search in the PUBMED.Use“sudden deafness”for the theme word to search in the CNKI.Results There are 381 articles in English,179 articles in Chinese.The article number of both database increase annually and the numbers are more than other years’in the 2012.(1)The top 3 countries published articles about sudden deafness in English are England,China,and Germany. The top 3 cities published articles about sudden deafness in Chinese are Guangdong,Henan,and Beijing.(2)There are 72(18.9%) articles about etiology of sudden deafness in English,61(16.0%) articles about diagnosis of sudden deafness in English,61(16.0%) articles about drug therapy.Articles about etiology and diagnosis in Chinese are less than in English.They focused in the therapy of sudden deafness. There are 61(34.1%) articles about drug therapy in Chinese,40(22.3%) articles about other therapy in Chinese,13(7.3%) about laboratory examination in Chinese.ConclusionThe hot spots of sudden deafness is significant different between home and abroad.The hot spots of sudden deafness is etiology,pathogenesis,and treatment.%目的:通过对PUBMED和CNKI数据库近5年收录的突聋研究文献检索、阅读和分析,了解近期突聋研究的热点问题和研究进展。方法在PUBMED数据库高级检索Mesh词表字段中检索“Hearing Loss,Sudden”,统计文献检索结果;在CNKI数据库主题字段中检索“突聋”,统计文献检索结果。结果 PUBMED及CNKI中近5年突聋文献发表数量呈逐年增加状态。共检索到英文文献381篇,中文文献179篇。①按地区分布看,英文文献数量前3位分别是英格兰、中国和德国。中文文献数量前3位分别是广东、河南和北京。②按文献研究方向看,英文文

  13. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    -molecule allosteric inhibitor trametinib in 2013, the progress of more than 10 other allosteric inhibitors in clinical trials, and the emergence of a pipeline of highly selective and potent preclinical molecules, have been reported in the past decade. In this article, we present the current knowledge on allosteric...

  14. Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.

    Science.gov (United States)

    Diaz-Franulic, Ignacio; Poblete, Horacio; Miño-Galaz, Germán; González, Carlos; Latorre, Ramón

    2016-07-01

    The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation. In this review we first discuss the allosteric coupling between the temperature and voltage sensor modules and the pore domain, and then discuss the thermodynamic foundations of thermo-TRP channel activation. We provide a structural overview of the molecular determinants of temperature sensing. We also posit an anisotropic thermal diffusion model that may explain the large temperature sensitivity of TRP channels. Additionally, we examine the effect of several ligands on TRP channel function and the evidence regarding their mechanisms of action. PMID:27297398

  15. Liver spots

    Science.gov (United States)

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... your skin by using skin bleaching lotions or creams. Most bleaching lotions use hydroquinone. This medicine is ...

  16. Allosteric Regulation of Phenylalanine Hydroxylase

    OpenAIRE

    Fitzpatrick, Paul F.

    2011-01-01

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  17. Four new WMO/GAW Observatories for the investigation of trace gas and aerosol variability in the Mediterranean hot-spot

    Science.gov (United States)

    Cristofanelli, Paolo; Marinoni, Angela; Duchi, Rocco; Busetto, Maurizio; Calzolari, Francescopiero; Bourcier, Laureline; Landi, Tony Christian; Calidonna, Claudia; Contini, Daniele; Ammoscato, Ivano; Gulli', Daniel; Dinoi, Adelaide; Sprovieri, Francesca; Carbone, Francesco; Naccarato, Attilio; Mannarino, Valentino; Pirrone, Nicola; Bonasoni, Paolo

    2016-04-01

    The Mediterranean Basin is considered a hot-spot region in term of air-quality and climate change due to the impact of anthropogenic and natural processes. Nevertheless, permanent infrastructures for the observations and the recognition of the atmospheric composition variability changes are still too sparse in this region. To contribute to a more accurate and wide-spread observation system, in the framework of the Project "I-AMICA" - Advanced Infrastructure for the Environmental-Climatic Monitoring (a three years Italian National Operative Program - PON, co-founded by the European Regional Development Fund), four permanent Climatic-Environmental Observatories have been set up in the southern Italy: Lecce (Apulia Region, 40° 20' 8" N, 18° 07' 28" E, 37 m a.s.l.), Lamezia Terme (Calabria Region, 38° 52' 34" N, 16° 13' 56" E, 6 m a.s.l.), Capo Granitola (Sicily, 37° 34' N, 12° 39' E, 5 m a.s.l.) and Mt. Curcio (Calabria, 39° 31' N, 16° 42' E, 1796 m a.s.l). These Observatories were equipped with homogeneous and standardized experimental set-up for measurements of aerosol properties (number size distribution, absorption and scattering coefficient, mass, equivalent black carbon), reactive and greenhouse gases (O3, NO, NO2, SO2, CO, CO2, CH4). The I-AMICA Observatories represent different conditions of the Mediterranean region, from suburban conditions at Lecce to costal background conditions at Lamezia Terme and Capo Granitola and high-mountain remote conditions at Mt. Curcio. The integration of the information from this high-quality observation network can be used for studies of aerosol transport from marine environment and Sahara desert, as well as for investigation of secondary pollutants formation in the gaseous and aerosol phase, investigation of continental outflow to Mediterranean Sea, impacts of vessel emissions on regional air quality and trans-boundary pollution. In this work, we provide a preliminary overview of gas and aerosol variability, together

  18. Converter Compressor Building, SWMU 089, Hot Spot Areas 1, 2, and 5 Operations, Maintenance, and Monitoring Report, Kennedy Space Center, Florida

    Science.gov (United States)

    Wilson, Deborah M.

    2015-01-01

    This Operations, Maintenance, and Monitoring Report (OMMR) presents the findings, observations, and results from operation of the air sparging (AS) interim measure (IM) for Hot Spot (HS) Areas 1, 2, and 5 at the Converter Compressor Building (CCB) located at Kennedy Space Center (KSC), Florida. The objective of the IM at CCB HS Areas 1, 2, and 5 is to decrease concentrations of volatile organic compounds (VOCs) in groundwater in the treatment zones via AS to levels that will enable a transition to a monitored natural attenuation (MNA) phase. This OMMR presents system operations and maintenance (O&M) information and performance monitoring results since full-scale O&M began in June 2014 (2 months after initial system startup in April 2014), including quarterly performance monitoring events in July and October 2014 and January and May 2015. Based on the results to date, the AS system is operating as designed and is meeting the performance criteria and IM objective. The performance monitoring network is adequately constructed for assessment of IM performance at CCB HS Areas 1, 2, and 5. At the March 2014 KSC Remediation Team (KSCRT) Meeting, team consensus was reached for the design prepared for expansion of the system to treat the HS 4 area, and at the November 2014 KSCRT Meeting, team consensus was reached that HS 3 was adequately delineated horizontally and vertically and for selection of AS for the remedial approach for HS 3. At the July 2015 KSCRT meeting, team consensus was reached to continue IM operations in all zones until HSs 3 and 4 is operational, once HS 3 and 4 zones are operational discontinue operations in HS 1, 2, and 5 zones where concentrations are less than GCTLs to observe whether rebounding conditions occur. Team consensus was also reached to continue quarterly performance monitoring to determine whether operational zones achieve GCTLs and to continue annual IGWM of CCB-MW0012, CCBMW0013, and CCB-MW0056, located south of the treatment area. The

  19. Regional scale analysis of nitrous oxide emissions within the U.S. Corn Belt and the potential role of episodic hot spots

    Science.gov (United States)

    Griffis, T. J.; Lee, X.; Baker, J. M.; Russelle, M.; Zhang, X.; Millet, D. B.; Venterea, R. T.

    2012-12-01

    Nitrous oxide (N2O) is a long-lived greenhouse gas that has the third largest radiative forcing on the Earth-Atmosphere system and has become the most important stratospheric ozone depleting substance of the 21st century. The rapid increase in N2O concentrations over the last century is primarily attributed to the Haber-Bosch process and the green revolution. Predicting future concentrations and developing mitigation strategies for N2O is a critical environmental challenge as pressure mounts on agricultural ecosystems to deliver more products to a burgeoning population. Bottom-up (process/inventory) and top-down (global) strategies are used to constrain the global N2O budget, but have been inadequately tested by data collected at the appropriate spatial and temporal scales. Two-years of tall tower (regional-scale) high-frequency N2O concentration data and boundary layer budget techniques were used to quantify the regional budget and assess bottom-up and top-down emission factors within the U.S. Corn Belt. Here we show that regional flux estimates were 2 to 9-fold greater than bottom-up emission estimates provided by the EDGAR, IPCC, and GEIA assessments. Using our regional flux data we derived "internal" and "external" emission factors that relate directly to the bottom-up and top-down perspectives on constraining the global N2O cycle. The internal and external emission factors were 4.0 and 5.6%, respectively, and significantly larger than that derived from bottom-up approaches. It is hypothesized that this bias is caused by episodic leakage mechanisms that can only be accounted for at the appropriate spatial and temporal scales.N2O emission hot spots from agricultural drainage ditches are shown to exceed 60 nmol m-2 s-1 and, at times, are about 60-fold greater than typical field-scale fluxes. Our data and analyses suggest that many field-scale studies that quantify greenhouse gas emissions will significantly underestimate the true net radiative forcing of

  20. "Ladies and Gentlemen, start your engines!" Analysis codes waiting for the first JIRAM-Juno data of Jupiter hot-spots

    Science.gov (United States)

    Grassi, Davide; Sindoni, Giuseppe; D'Aversa, Emiliano; Oliva, Fabrizio; Filacchione, Gianrico; Adriani, Alberto; Mura, Alessandro; Moriconi, Maria Luisa; Noschese, Raffaella; Cicchetti, Andrea; Piccioni, Giuseppe; Ignatiev, Nikolai; Maestri, Tiziano

    2016-04-01

    In this contribution, we detail the retrieval scheme that has been developed in the last few years for the analysis of the spectral data expected from the JIRAM experiment on board of the Juno NASA mission [1], beginning from the second half of 2016. Our focus is on the analysis of the thermal radiation in the 5 micron transparency window, in regions of lesser cloud opacity (namely, hot-spots). Moving from the preliminary analysis presented in Grassi et al., 2010 [2], a retrieval scheme has been developed and implemented as a complete end-to-end processing software. Performances in terms of fit quality and retrieval errors are discussed from tests on simulated spectra. Few examples of usage on VIMS-Cassini flyby data are also presented. Following the suggestion originally presented in Irwin et al., 1998 [3] for the analysis of the NIMS data, the state vector to be retrieved has been drastically simplified on physically sounding basis, aiming mostly to distinguish between the 'deep' content of minor gaseous component (water, ammonia, phosphine) and their relative humidity or fractional scale height in the upper troposphere. The retrieval code is based on a Bayesian scheme [4], complemented by a Metropolis algorithm plus simulated thermal annealing [5] for most problematic cases. The key parameters retrievable from JIRAM individual spectra are the ammonia and phosphine deep content, the water vapour relative humidity as well as the total aerosol opacity. We discuss in extent also the technical aspects related to the forward radiative transfer scheme: completeness of line databases used to generate correlated-k tables, comparison of different schemes for the treatment of aerosol scattering, assumption on clouds radiative properties and issues related to the analysis of dayside data. This work has been funded through ASI grants: I/010/10/0 and 2014-050-R.0. [1] Adriani et al., 2008 doi:10.1089/ast.2007.0167 [2] Grassi et al., 2010, doi: 10.1016/j.pss.2010.05.003 [3

  1. Research on the Dynamic Template Matching Method in Solar Energy Component Hot Spot Detection%太阳能组件热斑检测中的动态模板匹配方法研究

    Institute of Scientific and Technical Information of China (English)

    王阿勇; 杨静

    2012-01-01

    In order to decrease costs and effectively improve the component production qualities, thermal imagery is used to cany out the hot spot detection in solar energy components. The thermal images of solar energy components of large plate types are obtained in two times, and then they are spliced. In splicing thermal images, this paper suggests a splice algorithm based on the dynamic plate thermal images using the periodical properties shown by the component thermal images. Through corresponding tests, it can be proved that the algorithm can effectively improve component' s hot spot on-line detection efficiency. The designed detection scheme is adaptable to automatic hot spot detection with different specifications.%为了降低成本,有效提高组件的生产质量,利用热图像进行太阳能组件的热斑检测.分两次获取大板型太阳能组件热图像,然后进行图像拼接.在热图像的拼接中,利用组件热图像呈现周期性的特征,提出基于动态模板的热图像拼接算法.经过测试,动态模板的热图像拼接算法有效地提高了组件热斑在线检测效率,设计的检测方案适用于不同规格组件的热斑自动检测.

  2. Allosteric transition: a comparison of two models

    DEFF Research Database (Denmark)

    Bindslev, Niels

    2013-01-01

    Introduction Two recent models are in use for analysis of allosteric drug action at receptor sites remote from orthosteric binding sites. One is an allosteric two-state mechanical model derived in 2000 by David Hall. The other is an extended operational model developed in 2007 by Arthur Christopo......Introduction Two recent models are in use for analysis of allosteric drug action at receptor sites remote from orthosteric binding sites. One is an allosteric two-state mechanical model derived in 2000 by David Hall. The other is an extended operational model developed in 2007 by Arthur...

  3. Surface-Enhanced Raman Spectroscopy of Dye and Thiol Molecules Adsorbed on Triangular Silver Nanostructures: A Study of Near-Field Enhancement, Localization of Hot-Spots, and Passivation of Adsorbed Carbonaceous Species

    Directory of Open Access Journals (Sweden)

    Manuel R. Gonçalves

    2012-01-01

    Full Text Available Surface-enhanced Raman spectroscopy (SERS of thiols and dye molecules adsorbed on triangular silver nanostructures was investigated. The SERS hot-spots are localized at the edges and corners of the silver triangular particles. AFM and SEM measurements permit to observe many small clusters formed at the edges of triangular particles fabricated by nanosphere lithography. Finite-element calculations show that near-field enhancements can reach values of more than 200 at visible wavelengths, in the gaps between small spherical particles and large triangular particles, although for the later no plasmon resonance was found at the wavelengths investigated. The regions near the particles showing strong near-field enhancement are well correlated with spatial localization of SERS hot-spots done by confocal microscopy. Silver nanostructures fabricated by thermal evaporation present strong and fast fluctuating SERS activity, due to amorphous carbon contamination. Thiols and dye molecules seem to be able to passivate the undesired SERS activity on fresh evaporated silver.

  4. HOT SPOT STRESS ANALYSIS OF DIFFERENT GIRTH BUTT WELD DETAILS OF CAST STEEL JOINT%不同焊接构造的铸钢节点环形对接焊缝的热点应力分析

    Institute of Scientific and Technical Information of China (English)

    韩庆华; 郭琪; 林允昶; 邢颖

    2014-01-01

    铸钢节点与主体构件的环形对接焊缝处存在材料差异、几何差异和焊接残余应力,因此环形对接焊缝是铸钢节点疲劳破坏的重要研究对象。目前,国内对铸钢节点焊缝疲劳问题的研究比较缺乏,传统名义应力方法并不适用于铸钢节点。采用热点应力方法对铸钢节点环形对接焊缝的疲劳问题进行探究,比较4种热点应力外推方法的计算结果。为减小铸钢节点与主体构件不等壁厚对接焊缝产生的应力集中对疲劳性能的影响,分析对比了3种不同的焊接构造,并分别研究在壁厚t、径厚比d/t、壁厚比T/t三种参数影响下的热点应力变化规律。%The girth butt weld attaching to the cast steel joint and the hot-rolled tube are the important object of the fatigue study of the cast steel joint due to the material nonlinearity and geometric nonlinearity across the weld . However , the research on this issue rarely saw in China and the nominal stress method was not applicable to it .In the paper, the hot spot stress method was used while the results of hot spot stress extrapolations were compared .To reduce the impact of the stress concentration , different weld details were designed .The hot spot stress curve was drawn under consideration of the tube ’ s thickness and the other two parameters .

  5. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  6. Numerical simulation of the unsteady heat-transfer in a turbine-rotor in consideration of hot-spot effects. Final report; AG-Turbo-Vorhaben 1.324: Numerische Simulation des instationaeren Waermeuebergangs an einem Turbinenrotor unter Einschluss von Heissstellen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Nuernberger, D.

    2001-07-01

    In this research project the influence of hot-gas effects, so called hot-spots, to the thermal load of high pressure turbine rotors was investigated in. Generally the total process efficiency can massively be improved by an increase of the temperature level at turbine entrance. However the temperatures of modern gas turbines can only be realized by efficient cooling techniques of the turbine blade materials. Furthermore the turbine stages close to the combustion chamber are exposed to an additional thermal loading due to the so called hot-spots. These streaks of unburned fuel entering the first turbine passages can cause a dramatic increase of local temperature in their afterburning process. For an optimized thermal design a detailed knowledge of these hot-streaks and their interaction with the unsteady flow through the turbomachinery flow is necessary. With this research program time accurate numerical investigations were performed to analyze the interaction process between the occurring hot gases and the high loaded turbine rotors. The numerical simulations started with fundamental investigation of the hot-spot and heat transfer modeling. Based on these developements threedimensional time accurate simulations for a realistic high pressure turbine configuration were performed. Herein the unsteady mechanisms of the hot gases and their influence on the heat transfer of the blade material was analyzed. In total the hot-streaks lead to a massiv increase of the thermal loading mainly on the pressure sides. (orig.) [German] Im Rahmen dieses Forschungsvorhabens wurden der Einfluss von Heissgaseffekten, sogenannten Hot-Spots auf die thermische Belastung von Turbinenrotoren numerisch untersucht. Gemeinhin sind die sehr hohen Turbineneintrittstemperaturen, deren Erhoehung einen wesentlichen Beitrag zur Verbesserung des gesamten Prozesswirkungsgrades leisten, nur durch effektive Kuehlungsmassnahmen der Schaufelwerkstoffe realisierbar. Zudem erfahren diese unmittelbar dem

  7. Unraveling structural mechanisms of allosteric drug action.

    Science.gov (United States)

    Nussinov, Ruth; Tsai, Chung-Jung

    2014-05-01

    Orthosteric drugs block the active site to obstruct function; allosteric drugs modify the population of the active state, to modulate function. Available data lead us to propose that allosteric drugs can constitute anchors and drivers. The anchor docks into an allosteric pocket. The conformation with which it interacts is unchanged during the transition between the inactive and active states. The anchor provides the foundation that allows the driver to exert a 'pull' and/or 'push' action that shifts the receptor population from the inactive to the active state. The presence or absence of driver atom in an allosteric drug can exert opposite agonism. We map a strategy for driver identification and expect the allosteric trigger concept to transform agonist/antagonist drug discovery.

  8. 时事热点在大学英语教学中的德育教育功能%The Moral Education Function of Current Event Hot Spots in College English Teaching

    Institute of Scientific and Technical Information of China (English)

    杨剑; 王欣

    2015-01-01

    Based on the characteristics, functions and status quo of moral education in college English teaching, this paper takes three practical exploration considering current event hot spots in college English teaching: to assist college students to establish correct outlook in life and cultivate firm and indomitable perseverance; to cultivate students’ patriotism and national pride;to cultivate students’ careful, serious dedication to work and study. Current event hot spots can not only improve students’ interest in learning English, expand horizons, increase knowledge, but can have greater moral education to students in life outlook, patriotism, national pride, morality, history, culture and politics. To combine the current event hot spots with moral education in college English teaching, it is necessary to change the practice from single, non-organized individual behavior to unified, organized collective and integrated promotion.%基于大学英语教学中德育教育的特点、作用和现状,现结合时事热点在大学英语教学中推进德育教育的7个方面的研究内容,进行了三个方面的实践探索,即如何利用时事热点在大学英语教学中帮助学生树立正确人生观,培养坚韧不拔的毅力;培养学生爱国主义情怀和和民族自豪感和培养学生细致认真进行工作和学习的敬业精神。时事热点在大学英语教学的德育教育中不但能够提高学生学习英语的兴趣,扩大视野,增长知识,而且能够对学生进行系统、全面的关于人生观、爱国、民族自豪感、品德、历史、文化、政治等方面的大德育教育,所以应该把结合时事热点在大学英语教学推进德育教育的实践从单一的、无组织的教师个体行为逐渐向统一的、有组织的集体统筹推广的方向发展。

  9. Comparison of the chromosome maps around a resistance hot spot on chromosome 5 of potato and tomato using BAC-FISH painting

    NARCIS (Netherlands)

    Achenbach, U.C.; Tang, X.M.; Ballvora, A.; Jong, de H.; Gebhardt, C.

    2010-01-01

    Potato chromosome 5 harbours numerous genes for important qualitative and quantitative traits, such as resistance to the root cyst nematode Globodera pallida and the late blight fungus, Phytophthora infestans. The genes make up part of a “hot spot” for resistances to various pathogens covering a gen

  10. Modeling amperometric biosensors based on allosteric enzymes

    Directory of Open Access Journals (Sweden)

    Liutauras Ričkus

    2013-09-01

    Full Text Available Computational modeling of a biosensor with allosteric enzyme layer was investigated in this study. The operation of the biosensor is modeled using non-stationary reaction-diffusion equations. The model involves three regions: the allosteric enzyme layer where the allosteric enzyme reactions as well as then mass transport by diffusion take place, the diffusion region where the mass transport by diffusion and non-enzymatic reactions take place and the convective region in which the analyte concentration is maintained constant. The biosensor response on dependency substrate concentration, cooperativity coefficient and the diffusion layer thickness on the same parameters have been studied.

  11. Spatiotemporal distribution of the seismicity along the Mid-Atlantic Ridge north of the Azores from hydroacoustic data: Insights into seismogenic processes in a ridge-hot spot context

    Science.gov (United States)

    Goslin, J.; Perrot, J.; Royer, J.-Y.; Martin, C.; LourençO, N.; Luis, J.; Dziak, R. P.; Matsumoto, H.; Haxel, J.; Fowler, M. J.; Fox, C. G.; Lau, A. T.-K.; Bazin, S.

    2012-02-01

    The seismicity of the North Atlantic was monitored from May 2002 to September 2003 by the `SIRENA array' of autonomous hydrophones. The hydroacoustic signals provide a unique data set documenting numerous low-magnitude earthquakes along the section of the Mid-Atlantic Ridge (MAR) located in a ridge-hot spot interaction context. During the experiment, 1696 events were detected along the MAR axis between 40°N and 51°N, with a magnitude of completeness level ofmb≈ 2.4. Inside the array, location errors are in the order of 2 km, and errors in the origin time are less than 1 s. From this catalog, 15 clusters were detected. The distribution of source level (SL) versus time within each cluster is used to discriminate clusters occurring in a tectonic context from those attributed to non-tectonic (i.e. volcanic or hydrothermal) processes. The location of tectonic and non-tectonic sequences correlates well with regions with positive and negative Mantle Bouguer Anomalies (MBAs), indicating the presence of thinner/colder and thicker/warmer crust respectively. At the scale of the entire array, both the complete and declustered catalogs derived from the hydroacoustic signals show an increase of the seismicity rate from the Azores up to 43°30'N suggesting a diminishing influence of the Azores hot spot on the ridge-axis temperature, and well correlated with a similar increase in the along-axis MBAs. The comparison of the MAR seismicity with the Residual MBA (RMBA) at different scales leads us to think that the low-magnitude seismicity rates are directly related to along-axis variations in lithosphere rheology and temperatures.

  12. 热点应力法在汽车驱动桥焊接强度耐久性分析中的应用%Application of Hot Spot Stress Method on Welding Strength & Durability for Automotive Drive Axle

    Institute of Scientific and Technical Information of China (English)

    张娜; 魏德永; 曹征栋; 霍福祥

    2012-01-01

    According to structural characteristic of welded axle housing of automotive drive axle, simulation analysis is made to welded structural strength and durability with hot spot stress method and CAE technology. To verify the effectiveness of simulation of welding structure with hot spot stress method, test and simulation analysis are made to strength and durability of welding location of three types of standard welding components and two types of drive axle housing. The results show that the effectiveness of simulation of this method on stress of critical welding location is up to over 70%, the average of durability simulation life of the welding location is equivalent to test results.%针对汽车驱动桥焊接桥壳结构特点,采用热点应力法及CAE技术对其焊接结构强度耐久性进行了模拟分析.为验证热点应力法模拟焊接结构的有效性,对3种标准焊接件、2种驱动桥桥壳焊接部位的强度和耐久性进行了试验与模拟对比分析,结果表明,该方法对焊接部位关键点应力的模拟有效性达70%以上,焊接部位的耐久性模拟寿命均值与试验结果量级相当.

  13. 肺癌患者SPECT/CT同机融合显像肋骨单发病灶影像分析%SPECT/CT fusion imaging analysis of costal single hot spots in patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    包贺菊; 陈刚; 陈燕燕

    2014-01-01

    Objective To analyze the imaging features and clinical significance of solitary costal hot spots in patient with lung cancer on SPECT/CT fusion imaging and the value of low-dose CT for diagnosis.Methods SPECT/CT scan was performed on 68 patients with lung cancer and costal single hot spots using whole body bone imaging.The sites of lesions were classified into four types:junction between costal cartilage and rib,frontal rib,lateral rib,posterior rib.The shapes of lesions were classified into two forms:punctiform and strip shapes,and were analyzed and classified.The differences of the diagnosis of whole body bone imaging and SPECT/CT scan were analyzed.Results Punctiform spots were mainly due to costal fractures(36/68,52.94%).The majority of spots in strip shape were costal metastases (21/23,91.30%).The lesions of junction between costal cartilage and rib were punctiform shape and benign.Hot spots in posterior ribs were mainly costal metastases (18/22,81.82%).Sensitivity of diagnosis of the metastatic bone tumor with whole body bone imaging and SPECT/CT in single hot spot of spine and rib was 69.23% (18/26) and 92.31%(24/26),specificity 59.52%(25/42) and 85.71%(36/42),accuracy 63.24%(43/68) and 88.24% (60/68),positive predictive value 51.43% (18/35) and 80.00% (24/30),negative predictive value 75.76% (25/33) and 94.74% (36/38).SPECT/CT scan had differences with whole body bone imaging in sensitivity (P < 0.05),SPECT/CT scan had significant differences with whole body bone imaging in coincidence and specificity (P < 0.01).Conclusions Useful imaging features can be obtained from SPECT/CT fusion imaging with single costal hot spots,being helpful to differential diagnosis of benign and malignant lesions.SPECT/CT fusion imaging may improve the accuracy to diagnose the rib disease.%目的 分析肺癌患者SPECT/CT同机融合显像肋骨单发病灶的特征和临床诊断之间的相互关系,并评价定位CT在诊断中的作用.方法

  14. 超高强度热成形钢电阻点焊的数值模拟%Numerical Simulation in Resistance Spot Welding of Ultra-High Strength Hot-Formed Steel

    Institute of Scientific and Technical Information of China (English)

    郑文; 王敏; 孔谅; 程轩挺; 孙游; 雷鸣

    2012-01-01

    Based on the software SORPAS, an axial symmetric finite element model for the resistance spot welding process (RSW) of ultra-high strength hot-formed steel (UHSS) was established. By numerical simulation, change rules of the temperature field, the nugget size, etc during the spot welding were dis-covered quantitatively. Comparing the numerical simulation results with the experimental measured ones, it was proved that the finite element model is feasible. It can also provide guidance for the RSW process of the UHSS.%利用SORPAS软件对超高强度热成形钢板建立了描述点焊熔核形成过程的轴对称有限元模型.通过数值模拟,定量揭示了热成形钢点焊过程中温度场、熔核直径等过程量的变化规律.对比模拟计算与实测结果表明,该模型是可行的,可为超高强度热成形钢的电阻点焊提供指导.

  15. Hot spot stress analysis of girth butt weld in cast steel joint%铸钢节点环形对接焊缝热点应力分析

    Institute of Scientific and Technical Information of China (English)

    韩庆华; 陈志钢; 芦燕

    2011-01-01

    铸钢节点的壁厚大于连接杆件,两者连接时壁厚方向存在几何形状的突变,引起焊缝附近的应力集中,降低其疲劳性能。目前现行规程或标准针对铸钢节点与主体结构连接处焊缝的疲劳问题没有明确的设计规定。本文选取两种焊接构造,采用热点应力的表面线性外推法对环形对接焊缝进行轴力作用下的疲劳性能有限元分析。同时选取结构杆件的壁厚t、径厚比d/t以及铸钢与普通杆件的壁厚比T/t作为热点应力的影响因素进行参数分析。分析结果表明:热点应力与厚度t关系不大,随着ln(d/t)的增大热点应力呈线性增加;随着T/t的增加,热点应力先增大后减小;ln(σ/(T/t))随着T/t的增加呈线性减小。%As cast steel joints are thicker than the hot-rolled tubes attached,sharp transition in the direction of thickness would cause stress concentration and weaken its fatigue performance.At present,there are no regulations or standards to guide the design of girth butt weld's fatigue behavior of cast steel joints.A hot-spot stress FEM analysis of weld's fatigue behavior was conducted based on the surface extrapolation method in this paper,considering two kinds of welding details under axial loads.Parametric analysis were carried out on the thickness(t) of hot-rolled tube,the ratio of tube's diameter to its thickness(d/t) and the ratio of cast steel joint's thickness to tube's(T/t).The results show that although the hot-spot stress is independent of the thickness of tubes(t),it will increase linearly with the increment of ln(d/t) and increase firstly then decrease with the increment of T/t.In addition,ln(σ/(T/t))(σ means the hot-spot stress) decreases linearly with the increment of T/t.

  16. Chemogenomics of allosteric binding sites in GPCRs

    DEFF Research Database (Denmark)

    Gloriam, David E.

    2013-01-01

    profiling. This review describes recent developments structured into ligand-, target- and combined chemogenomic techniques and applications to allosteric GPCR ligands. It also outlines relative strengths and limitations of these techniques and the impact of the increasing crystallographic data....

  17. Parameter optimization of dissimilar resistance spot welding on ultra-high strength hot-stamped steel and mild steel by numerical simulation

    Institute of Scientific and Technical Information of China (English)

    Wen ZHENG; Min WANG; Liang KONG; Xuanting CHENG; Ming LEI

    2012-01-01

    In this study,a coupled axisymmetric finite element model (FEM) was built to simulate the resistance spot welding (RSW) process between ultra-high strength hotstamped (UHSS) and mild steel by SORPAS software.Via simulating this process,the temperature distribution and dynamic temperature curves of the welding area were studied,and welding spatter phenomena were predicted and validated by comparing them with experimental results.By adjusting the welding parameters in numerical simulation,appropriate welding parameters were achieved.Moreover,the mechanical properties of the welding joints under the optimized conditions were also compared with those of not optimized.The study results have already been applied in a manufacturing production.It can also provide guidance for the RSW on UHSS and mild steel.

  18. 以箱壁温度为判据的油浸式变压器绕组热点温度计算模型及试验分析%Model of Hot Spot Temperature in Oil-immersed Transformers Using Temperature Estimation of Tank Wall

    Institute of Scientific and Technical Information of China (English)

    李剑; 刘兴鹏; 王有元; 陈伟根; 邓宗权

    2011-01-01

    电力变压器的热点温度是影响其绝缘寿命非常重要的因素,准确估计电力变压器热点温度,有助于提高电力变压器的经济与安全运行水平。为此,提出了一种估计变压器绕组热点温度的改进方法。该方法依据变压器热路模型,采用变压器油箱壁温度来估计绕组热点温度。为了验证该方法的准确性,在实验室的试验变压器上进行了负载试验,得到不同负载下的变压器绕组热点温度和油箱壁温度的实测值,并将热点温度的实测结果与该方法计算值以及IEEE负载导则公式的计算值进行了比较。分析结果表明,改进方法具有较小的热点温度估计误差,证明了改进方法估计变压器热点温度的有效性。%Hot spot temperature is a very important factor that influences lifetime of insulation in power transtormers. Accurate estimation of the hot spot temperatures of transformer windings is helpful to improving economic and safe operation levels of transformers. Consequently, an improved approach was presented to estimate hot spot temperatures of transformer windings. The improved approach was based on a thermal circuit of power transformers. Temperatures of transformer wails were used to estimate the hot spot temperature of transformer windings, and load of transformers was tested in laboratory to obtain the measurement data of temperatures of hot spot and transformer walls. The measurement results were compared with the estimated results of the improved approach and the calculated results of IEEE loading guide equations. The analysis results show that the improved approach has smaller estimation errors of hot spot temperature than the IEEE load guide equations. The improved approach is verified to be effective for estimation of hot spot temperature in transformers.

  19. Bier spots

    Directory of Open Access Journals (Sweden)

    Ahu Yorulmaz,

    2015-10-01

    Full Text Available Also called as physiologic anemic macules, Bier spots are small, hypopigmented irregularly shaped macules against a background of diffuse erythema, which creates an appearance of speckled vascular mottling of the skin. Bier spots most commonly appear on distal portions of the limbs though there are case reports describing diffuse involvement, which also affect trunk and mucous membranes of the patient. Although the exact pathophysiological mechanisms underlying Bier spots still need to be elucidated, Bier spots have been suggested to be a vascular anomaly caused by vasoconstriction of small vessels. In addition, several diseases have been proposed to be associated with Bier spots, including scleroderma renal crisis, cryoglobulinemia, Peutz-Jeghers syndrome, alopecia areata and hypoplasia of the aorta, although it has not been shown whether these associations are casual or coincidental. The clinical presentation of Bier spots is quite typical. These tiny whitish macules easily become prominent when the affected limb is placed in a dependent position and fade away when the limb is raised. Here we report a case of Bier spots in a 32-year-old male patient with characteristical clinical manifestations.

  20. 国外足球耐力热点研究及其变化趋势分析%Research on the Hot Spots of Football Endurance in Foreign Countries and the Analysis of Its Changing Trend

    Institute of Scientific and Technical Information of China (English)

    陈小虎; 黄竹杭; 李春满

    2016-01-01

    以Web of ScienceTM核心合集数据库中(SCIE、SSCI和 A&HCI )收录的1997—2015年以足球耐力为主题的488篇文献信息作为数据源,运用科学知识图谱技术分析国外足球耐力研究的国家、机构和作者分布,并通过解析当前足球耐力研究的关键词,揭示国外足球耐力研究的相关热点以及其变化趋势。研究发现:美国的发文量最大,但英国所发文章的中心性更高,发文的机构主要集中在高等院校;来自各高等院校的Karim Chamari、Anis Chaoua‐chi、Peter Krustrup等教授是研究足球耐力的突出作者;研究的热点主要包括运动训练、竞技表现、训练方法和测试方法的可靠性、训练负荷及运动员的训练反应等;变化趋势以运动员训练和竞技表现为主线,由运动员身体反应过渡到检验测试方法的可靠性,再由关注训练方法的有效性过渡到利用先进技术分析运动员在训练和比赛中的表现。现阶段的足球耐力研究多为方法性研究,研究大多基于足球训练或比赛中的外在表现形成,缺乏支撑训练和比赛的基础性理论研究。%Selecting the literature from Web of ScienceTM core collection database (SCIE ,and SSCI and A&HCI) ,and taking the 488 articles during 1997—2015 with the theme of foot‐ball endurance as data source ,using knowledge map technology to analysis the football endur‐ance research study of foreign countries ,institutions and the distribution of authors ,and by re‐solving the current football endurance research keywords ,reveal the abroad study on the endur‐ance of football‐related hot spots and trends .The result shows that United States is issued much more than other countries ,but the most centrality is England .The institutions of issued mainly concentrated in university ;the professor of Karim Chamari ,Anis Chaouachi ,and Peter Krustrup from respective university are the highlight author to research

  1. An improved dynamic model of transformer hot spot temperature based on top oil temperature%基于顶层油温的变压器绕组热点温度计算改进模型

    Institute of Scientific and Technical Information of China (English)

    陈伟根; 苏小平; 周渠; 潘翀; 谢波

    2012-01-01

    油浸式电力变压器绕组热点温度是影响变压器绝缘寿命的重要参量,与变压器顶层油温密切相关。考虑非线性热阻一变压器断路阻抗、油粘滞度以及绕组损耗随温度的变化,引入粘滞度与损耗关于温度变化的修正因子,提出一种基于顶层油温的变压器绕组热点温度改进模型。模型参数选用Levenberg-Marquardt算法进行估算。对比实验室温升用试验变压器实测数据,该模型在欠负载(90%)、额定负载(100%)以及过负载(110%)下,显示了较好的一致性,特别在动态负载下,能够较好地描述各暂态温度变化情况,为变压器绕组热点温度计算提出了一种新方法。%The winding hot spot temperature of the oil-immersed power transformer is an important parameter. It has a great influence on the transformer insulation aging and a close relationship with the transformer top oil temperature. The changes of non-linear thermal resistance, open-circuit impedance, and oil viscosity and winding losses with temperature are also taken into account. An improved model added on the transformer top oil temperature to calculate transformer winding hot-spot temperature by using the viscosity and loss correction factors is proposed. Model parameters are estimated by Levenberg-Marquardt method. In the end, by comparing with the measured data tested under different conditions, the model shows good consistency under underload (90%), rated load (100%) and overload (110%) conditions respectively, and describes the temperature variation more accurately in the dynamic loading profiles.

  2. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    International Nuclear Information System (INIS)

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi2Sr2CaCu2O8+δ by Chatterjee et al. [Nature Phys. 6 (2010) 99], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model such that only eight points located near the “hot spots” on the Fermi surface are retained, which are directly connected by spin density wave ordering wavevector. We derive RG equations up to two-loop order describing the flow of renormalized couplings, quasiparticle weight, several order-parameter response functions, and uniform spin and charge susceptibilities of the model. We find that while the order-parameter susceptibilities investigated here become non-divergent at two loops, the quasiparticle weight vanishes in the low-energy limit, indicating a breakdown of Fermi liquid behavior at this RG level. Moreover, both uniform spin and charge susceptibilities become suppressed in the scaling limit which indicate gap openings in both spin and charge excitation spectra of the model

  3. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    Science.gov (United States)

    de Carvalho, Vanuildo S.; Freire, Hermann

    2013-10-01

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi2Sr2CaCu2O8 + δ by Chatterjee et al. [Nature Phys. 6 (2010) 99], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model such that only eight points located near the “hot spots” on the Fermi surface are retained, which are directly connected by spin density wave ordering wavevector. We derive RG equations up to two-loop order describing the flow of renormalized couplings, quasiparticle weight, several order-parameter response functions, and uniform spin and charge susceptibilities of the model. We find that while the order-parameter susceptibilities investigated here become non-divergent at two loops, the quasiparticle weight vanishes in the low-energy limit, indicating a breakdown of Fermi liquid behavior at this RG level. Moreover, both uniform spin and charge susceptibilities become suppressed in the scaling limit which indicate gap openings in both spin and charge excitation spectra of the model.

  4. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Vanuildo S. de [Instituto de Física, Universidade Federal de Goiás, 74.001-970 Goiânia, GO (Brazil); Freire, Hermann, E-mail: hfreire@mit.edu [Instituto de Física, Universidade Federal de Goiás, 74.001-970 Goiânia, GO (Brazil); Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2013-10-21

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+} {sub δ} by Chatterjee et al. [Nature Phys. 6 (2010) 99], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model such that only eight points located near the “hot spots” on the Fermi surface are retained, which are directly connected by spin density wave ordering wavevector. We derive RG equations up to two-loop order describing the flow of renormalized couplings, quasiparticle weight, several order-parameter response functions, and uniform spin and charge susceptibilities of the model. We find that while the order-parameter susceptibilities investigated here become non-divergent at two loops, the quasiparticle weight vanishes in the low-energy limit, indicating a breakdown of Fermi liquid behavior at this RG level. Moreover, both uniform spin and charge susceptibilities become suppressed in the scaling limit which indicate gap openings in both spin and charge excitation spectra of the model.

  5. Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis

    OpenAIRE

    Jae-Seong Yang; Sang Woo Seo; Sungho Jang; Gyoo Yeol Jung; Sanguk Kim

    2012-01-01

    Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligan...

  6. Age Spots

    Science.gov (United States)

    ... for treating age spots include: Improved appearance. Enhanced self-esteem. Promotion of better skin health. What you need ... 480px View Render 320px View Connect with ASDS: Facebook LinkedIn YouTube Twitter Quick Links About ASDS Advocacy ...

  7. Characterizing seasonal variability of storm events based on very high frequency monitoring of hydrological and chemical variables: comparing patterns in hot spots and hot moments for nutrient and sediment export

    Science.gov (United States)

    Fovet, Ophelie; Thelusma, Gilbert; Humbert, Guillaume; Dupas, Rémi; Faucheux, Mikael; Gilliet, Nicolas; Hamon, Yannick; Jaffrezic, Anne; Grimaldi, Catherine; Gruau, Gerard

    2016-04-01

    Storm events are critical hot moments of emission for several dissolved and particulate chemical species at major stake for water quality (e.g. dissolved organic carbon DOC, suspended sediments, phosphorus). During such events, the solutes or particles are exported from heterogeneous sources through various pathways to stream leading to specific integrated signals at the outlet characterized by very short dynamics. This is merely true in headwater catchments where the total duration of such events ranges over 10h to 3 days, with very quick variations in stream flow and concentrations at the outlet occurring in a few hours. Thus for investigating properly event processes, high frequency monitoring of flow and water quality is required. We analysed 103 storm events in a 5 km2 agricultural headwater catchment, part of the AgrHys Observatory, on the basis of a 3-year-long data set which combined meterological (Rainfall), hydrological (flow and piezometry), and water quality (turbidity, conductivity, DOC and NO3 concentrations) data recorded at very high frequencies (from 1 to 20 min) thanks to dedicated sensors. We proposed a range of quantitative storm descriptors for characterizing input (rainfall), antecedent and initial conditions (groundwater levels and saturated area), and stream response in terms of level and dynamics of flow (Q), groundwater levels, and concentrations (C) but also the C-Q relationships. Three intra annual periods have been previously defined for base flow dynamic according to shallow groundwater table variations so that they correspond to different connectivity status in the catchment. The seasonal and inter-annual variability of the storm events have been analysed using the descriptors and based on these predefined periods. Results show that the hydrological flowpaths and the consequent storm chemistry were controlled by the hydrological base flow regime rather than by the rain input characteristics. This highlights that the exports of NO3

  8. Detecting Allosteric Networks Using Molecular Dynamics Simulation.

    Science.gov (United States)

    Bowerman, S; Wereszczynski, J

    2016-01-01

    Allosteric networks allow enzymes to transmit information and regulate their catalytic activities over vast distances. In principle, molecular dynamics (MD) simulations can be used to reveal the mechanisms that underlie this phenomenon; in practice, it can be difficult to discern allosteric signals from MD trajectories. Here, we describe how MD simulations can be analyzed to reveal correlated motions and allosteric networks, and provide an example of their use on the coagulation enzyme thrombin. Methods are discussed for calculating residue-pair correlations from atomic fluctuations and mutual information, which can be combined with contact information to identify allosteric networks and to dynamically cluster a system into highly correlated communities. In the case of thrombin, these methods show that binding of the antagonist hirugen significantly alters the enzyme's correlation landscape through a series of pathways between Exosite I and the catalytic core. Results suggest that hirugen binding curtails dynamic diversity and enforces stricter venues of influence, thus reducing the accessibility of thrombin to other molecules. PMID:27497176

  9. Computation of conformational coupling in allosteric proteins.

    Directory of Open Access Journals (Sweden)

    Brian A Kidd

    2009-08-01

    Full Text Available In allosteric regulation, an effector molecule binding a protein at one site induces conformational changes, which alter structure and function at a distant active site. Two key challenges in the computational modeling of allostery are the prediction of the structure of one allosteric state starting from the structure of the other, and elucidating the mechanisms underlying the conformational coupling of the effector and active sites. Here we approach these two challenges using the Rosetta high-resolution structure prediction methodology. We find that the method can recapitulate the relaxation of effector-bound forms of single domain allosteric proteins into the corresponding ligand-free states, particularly when sampling is focused on regions known to change conformation most significantly. Analysis of the coupling between contacting pairs of residues in large ensembles of conformations spread throughout the landscape between and around the two allosteric states suggests that the transitions are built up from blocks of tightly coupled interacting sets of residues that are more loosely coupled to one another.

  10. 基于CiteSpace的教育大数据研究热点与趋势分析%The Analysis of Research Hot Spot and Trend on Big Data in Education based on CiteSpace

    Institute of Scientific and Technical Information of China (English)

    王娟; 陈世超; 王林丽; 杨现民

    2016-01-01

    With the era of big data coming, huge amount of data has been accumulated in education field. Taking CNKI and Google as research object, which including 924 and 204 journal papers about big Data in education respectively, adopting knowledge map of time and space and content knowledge map as main research methods, and applying the information visualization software CiteSpace, research hot spot and development trend of big data in education were revealed. It found the research of big data in education presented the following features: from the perspective of time, the research began to emerge centrally in 2013, and entered the stage of large-scale development in 2014-2015; from the view of content, the hot topic has “big data”, “big data era”, “study analysis and technology”, “data mining”, and etc. The further summary and reflection were given, in order to provide reference for deep study, practical exploration and industry promotion of big data in education.%大数据时代来临,教育领域积累了海量数据。文章以中国知网(CNKI)数据库收录的924篇及 Google学术收录的204篇与教育大数据相关的期刊论文为研究对象,运用信息可视化软件CiteSpace,以时空知识图谱及内容知识图谱分析为主要研究方法,揭示了国内外教育大数据的研究热点及发展趋势。分析发现,教育大数据研究呈现如下特点:从时间上看,研究在2013年开始集中涌现,2014~2015年进入大规模发展阶段;从内容上看,研究热点有“大数据”、“大数据时代”、“学习分析及技术”、“数据挖掘”等。为此,文章给出进一步的总结和思考,以期为教育大数据的深入研究、实践探索和产业推进提供参考。

  11. Thickness of the oceanic crust and the mantle transition zone in the vicinity of the Tristan da Cunha hot spot estimated from ocean-bottom and ocean-island seismometer receiver functions

    Science.gov (United States)

    Geissler, Wolfram; Jokat, Wilfried; Jegen, Marion; Baba, Kiyoshi

    2016-04-01

    According to classical plume theory, the Tristan da Cunha hotspot is thought to have played a major role in the rifting of the South Atlantic margins and the creation of the aseismic Walvis Ridge by impinging at the base of the continental lithosphere shortly before or during the breakup of the South Atlantic margins. However, Tristan da Cunha is enigmatic as it cannot be clearly identified as a hot spot but may also be classified as a more shallow type of anomaly that may actually have been caused by the opening of the South Atlantic. The equivocal character of Tristan da Cunha is largely due to a lack of geophysical and petrological data in this region. We therefore staged a multi-disciplinary geophysical study of the region by acquiring passive marine electromagnetic and seismic data, and bathymetric data within the framework of the SPP1375 South Atlantic Margin Processes and Links with onshore Evolution (SAMPLE) funded by the German Science foundation. The experiment included two ship expeditions onboard the German R/V MARIA S. MERIAN in 2012 and 2013. In our contribution we will present results on the thickness of the oceanic crust in the vicinity of the Tristan da Cunha archipelago derived from ocean-bottom seismometer data. Using the Ps receiver function method we estimate a thickness of 5 to 7 km for the oceanic crust at 17 ocean-bottom stations surrounding the islands in an area where the ocean floor has an age of approximately 10 to 30 Ma (from west to east). This indicates normal to slightly lowered magmatic activity at the mid-ocean ridge during the crust formation. There seems to be no major contribution of a mantle plume to the melting conditions at the ridge, which should cause the formation of thickened oceanic crust. The magmatic activity at the archipelago and surrounding seamounts seems to have only local effects on the crustal thickness. Furthermore, we imaged the mantle transition zone discontinuities analysing receiver functions at the

  12. Automated direct sequencing of the iduronate-2 sulfatase gene reveals a vast spectrum of mutations causing Hunter syndrome (mucopolysaccharidosis type II) and a {open_quotes}hot spot{close_quotes} at R468

    Energy Technology Data Exchange (ETDEWEB)

    Whitley, C.B; Jonsson, J.J.; Aronovich, E.L. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)

    1994-09-01

    Hunter syndrome is an X-linked recessive, lethal disease resulting from deficiency of iduronate-2-sulfatase (IDS) catalytic activity. Because of low reproductive fitness, most affected individuals are expected to have new mutations. Most of such defects are anticipated to be single base pair (bp) changes; however, several previous studies utilizing Southern analysis of RT-PCR have identified numerous large gene deletions in patients having the {open_quotes}severe form{close_quotes} with neurologic disease. To investigate the spectrum of IDS mutations, we have developed a method of automated direct sequencing of RT-PCR products representing the entire IDS coding region. Of 19 patients studied by this approach, only 1 had an IDS coding region which did not contain a mutation; 1 had a single bp insertion; 1 had a 2 bp deletion; and 13 had single-base substitutions. Of the 13 having single base substitutions, 2 resulted in aberrant splicing. Only 1 patient had a complete gene deletion; in view of previous reports, there was a surprising lack of major gene deletions. Notably, a CpG dinucleotide at R468 was identified as a {open_quotes}hot spot{close_quotes} for mutation. Five unrelated individuals had substitutions at this site which thus accounted for 28% of all mutations in this series: R468W (3 patients) and R468Q (2 patients). MspI digestion provided a method of rapid diagnosis and determination of heterozygote status for such R468 mutations. Genotype-phenotype correlations in this R468 group are not yet possible because of confounding information, i.e., there are both {open_quotes}mild{close_quotes} and {open_quotes}severe{close_quotes} patients in this group and some have co-existing neurologic diseases. This approach of gene sequencing appears to be necessary, and sufficient, to characterize the vast spectrum of mutations in Hunter syndrome.

  13. 从医院管理几个热点问题谈医疗服务质量%Analysis of Medical Service Quality from Several Hot Spots of Hospital Management

    Institute of Scientific and Technical Information of China (English)

    易学明

    2011-01-01

    Medical service quality is the core and etemal theme of hospital management. The article deeply discussed the improvement of medical service quality from five aspects, which included correctly treat the conflict of social responsibility and self - profit so as to convert the thought of medical service; rightly recognize the problem of reasonable scale and exceed expansion so as to enhance inherent medical quality; erect the idea of service con-sciousness and service art so as to master the communication skiU; objectively handle the relationship of high - techand basic quality so as to fulfill the increasing requirement. We expect to focus on the improvement of medical serv-ice quality from the several hot spots to promote the hospital sustainable and healthy development.%医疗服务质量是医院管理的核心和永恒主题,本文从合理解决社会责任与自身利益的矛盾,转变医疗服务理念;正确看待过度扩张与适度规模的现象,加强内涵质量建设;科学树立以病为本与以人为本的理念,优化医疗服务流程;极力实现服务意识与服务艺术的交融,掌握医患沟通技巧;客观认识高新技术与基础质量的关系,满足持续发展需求五个方面就医疗服务质量建设进行了深入的探讨.以期从医院管理的几个热点问题来关注医疗服务质量,促进医院健康持续快速发展.

  14. 3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline inhibits pestivirus replication by targeting a hot spot drug binding pocket in the RNA-dependent RNA polymerase.

    Science.gov (United States)

    Musiu, Simone; Leyssen, Pieter; Froeyen, Mathy; Chezal, Jean-Michel; Neyts, Johan; Paeshuyse, Jan

    2016-05-01

    The compound 3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline (CF02334) was identified as a selective inhibitor of the cytopathic effect (CPE) caused by bovine viral diarrhea virus (BVDV) in a virus-cell-based assay. The EC50-values for inhibition of CPE, viral RNA synthesis and the production of infectious virus progeny were 13.0 ± 0.6 μM, 2.6 ± 0.9 μM and 17.8 ± 0.6 μM, respectively. CF02334 was found to be inactive in the hepatitis C subgenomic replicon system. CF02334-resistant BVDV was obtained and was found to carry the N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). Molecular modeling revealed that N264D is located in a small cavity near the fingertip domain of the pestivirus polymerase. CF02334-resistant BVDV was proven to be cross-resistant to BPIP, AG110 and LZ37, inhibitors that have previously been described to target the same region of the BVDV RdRp. CF02334 did not inhibit the in vitro activity of recombinant BVDV RdRp, but did inhibit the activity of BVDV replication complexes. Taken together, these observations indicate that CF02334 likely interacts with the fingertip of the pestivirus RdRp at the same position as BPIP, AG110 and LZ37, which marks this region of the viral polymerase as a "hot spot" for inhibition of pestivirus replication. PMID:26970496

  15. 铜锌超氧化物歧化酶知识基础及前沿热点分析%Knowledge base, research front and hot spot analysis of Cu-Zn superoxide dismutase

    Institute of Scientific and Technical Information of China (English)

    邹昱; 李彦君; 杨爽; 张庆文

    2015-01-01

    genetics. So far more than 100 kinds of SOD1 gene mutations have been found. OBJECTIVE:To analyze the hot spot, research front and knowledge base of amyotrophic lateral sclerosis visualy. METHODS:Totaly 4 693 relevant articles published from 2005 to 2014 were retrieved from Web of Science in ISI with “Cu-Zn superoxide dismutase” or “SOD1” as search keywords. With the aid of CiteSpace III software, the visualization mapping of the network in co-cited articles and keywords was drawn to reveal knowledge base, hot spots and research front of SOD1. The parameters include the number of published papers and citations within 10 years, distribution of research countries and institutions, main source journals, research area of highly cited papers, keywords with high-frequency and emerging keywords with high-frequency in recent 5 years. RESULTS AND CONCLUSION:The number of published papers and citations in a year showed a trend of sustained growth. United State, China and Japan rank the top three in this area, in which Chinese Academy of Sciences has a great influence among the research institutions. The research fields of SOD1 focus on neurosciences and neurology, biochemistry and molecular biology and so on. The high impact factors of journals with a large number of articles reflect the importance and innovation of this research. Ten high-cited articles consist of the knowledge base on SOD1, directing to the finding of different sites of SOD1 mutation and the measurement of protein concentrations and activity of SOD. The hot spots of SOD1 mainly focus on oxidative stress, familial amyotrophic lateral sclerosis caused by SOD1 mutation and different types of transgenic animal models. The research fronts mainly focus on the finding of pathogenesis in amyotrophic lateral sclerosis, such as the aggregation of TDP-43, the interaction between astrocytes and motor neurons, optineurin and the inhibitor of nuclear factor-κB, hexanucleotide repeat expansion in C9ORF72 and autophagy.

  16. Mongolian spots

    Directory of Open Access Journals (Sweden)

    Divya Gupta

    2013-01-01

    Full Text Available Mongolian spots (MS are birthmarks that are present at birth and their most common location is sacrococcygeal or lumbar area. Lesions may be single or multiple and usually involve < 5% total body surface area. They are macular and round, oval or irregular in shape. The color varies from blue to greenish, gray, black or a combination of any of the above. The size varies from few to more than 20 centimetres. Pigmentation is most intense at the age of one year and gradually fades thereafter. It is rarely seen after the age of 6 years. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although regarded as benign, recent data suggest that MS may be associated with inborn errors of metabolism and neurocristopathies. Mongolian spots usually resolve by early childhood and hence no treatment is generally needed if they are located in the sacral area. However, sometimes it may be required for extrasacral lesions for cosmesis.

  17. Design of an allosterically regulated retroaldolase

    Science.gov (United States)

    Raymond, Elizabeth A; Mack, Korrie L; Yoon, Jennifer H; Moroz, Olesia V; Moroz, Yurii S; Korendovych, Ivan V

    2015-01-01

    We employed a minimalist approach for design of an allosterically controlled retroaldolase. Introduction of a single lysine residue into the nonenzymatic protein calmodulin led to a 15,000-fold increase in the second order rate constant for retroaldol reaction with methodol as a substrate. The resulting catalyst AlleyCatR is active enough for subsequent directed evolution in crude cell bacterial lysates. AlleyCatR's activity is allosterically regulated by Ca2+ ions. No catalysis is observed in the absence of the metal ion. The increase in catalytic activity originates from the hydrophobic interaction of the substrate (∼2000-fold) and the change in the apparent pKa of the active lysine residue. PMID:25516403

  18. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    Directory of Open Access Journals (Sweden)

    Hall David A

    2008-07-01

    colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential.

  19. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    International Nuclear Information System (INIS)

    Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02). Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for

  20. Rational engineering of enzyme allosteric regulation through sequence evolution analysis.

    Directory of Open Access Journals (Sweden)

    Jae-Seong Yang

    Full Text Available Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligand-binding sites. We found that allosteric sites are evolutionarily variable and comprised of more hydrophobic residues than catalytic sites. We applied our findings to design mutations in selected target residues that deregulate the allosteric activity of fructose-1,6-bisphosphatase (FBPase. Specifically, charged amino acids at less conserved positions were substituted with hydrophobic or neutral amino acids with similar sizes. The engineered proteins successfully diminished the allosteric inhibition of E. coli FBPase without affecting its catalytic efficiency. We expect that our method will aid the rational design of enzyme allosteric regulation strategies and facilitate the control of metabolic flux.

  1. Polypharmacology within CXCR4: Multiple binding sites and allosteric behavior

    Science.gov (United States)

    Planesas, Jesús M.; Pérez-Nueno, Violeta I.; Borrell, José I.; Teixidó, Jordi

    2014-10-01

    CXCR4 is a promiscuous receptor, which binds multiple diverse ligands. As usual in promiscuous proteins, CXCR4 has a large binding site, with multiple subsites, and high flexibility. Hence, it is not surprising that it is involved in the phenomenon of allosteric modulation. However, incomplete knowledge of allosteric ligand-binding sites has hampered an in-depth molecular understanding of how these inhibitors work. For example, it is known that lipidated fragments of intracellular GPCR loops, so called pepducins, such as pepducin ATI-2341, modulate CXCR4 activity using an agonist allosteric mechanism. Nevertheless, there are also examples of small organic molecules, such as AMD11070 and GSK812397, which may act as antagonist allosteric modulators. Here, we give new insights into this issue by proposing the binding interactions between the CXCR4 receptor and the above-mentioned allosteric modulators. We propose that CXCR4 has minimum two topographically different allosteric binding sites. One allosteric site would be in the intracellular loop 1 (ICL1) where pepducin ATI-2341 would bind to CXCR4, and the second one, in the extracellular side of CXCR4 in a subsite into the main orthosteric binding pocket, delimited by extracellular loops n° 1, 2, and the N-terminal end, where antagonists AMD11070 and GSK812397 would bind. Prediction of allosteric interactions between CXCR4 and pepducin ATI-2341 were studied first by rotational blind docking to determine the main binding region and a subsequent refinement of the best pose was performed using flexible docking methods and molecular dynamics. For the antagonists AMD11070 and GSK812397, the entire CXCR4 protein surface was explored by blind docking to define the binding region. A second docking analysis by subsites of the identified binding region was performed to refine the allosteric interactions. Finally, we identified the binding residues that appear to be essential for CXCR4 (agonists and antagonists) allosteric

  2. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.

    Science.gov (United States)

    Christopoulos, Arthur; Changeux, Jean-Pierre; Catterall, William A; Fabbro, Doriano; Burris, Thomas P; Cidlowski, John A; Olsen, Richard W; Peters, John A; Neubig, Richard R; Pin, Jean-Philippe; Sexton, Patrick M; Kenakin, Terry P; Ehlert, Frederick J; Spedding, Michael; Langmead, Christopher J

    2014-10-01

    Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

  3. Hot Money, Hot Potato

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    International hot money flowing into Chinese capital markets has caught the attention of Chinese watchdogs The Chinese are not the only ones feasting on the thriving property and stock markets. Apparently, these markets are the targets of international h

  4. Calculated pKa Variations Expose Dynamic Allosteric Communication Networks.

    Science.gov (United States)

    Lang, Eric J M; Heyes, Logan C; Jameson, Geoffrey B; Parker, Emily J

    2016-02-17

    Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator.

  5. An allosteric model for the functional plasticity of olfactory chemoreceptors

    Science.gov (United States)

    Colosimo, Alfredo

    2000-12-01

    A simple allosteric model may describe the relatively (a)specific behaviour of olfactory chemoreceptors (OCs) and their functional plasticity with a minimum number of parameters. Allosteric, heterotropic effectors are suggested as a possible cause of variable responses documented, in particular, in frog OCs. As an immediate spinoff of the continuously increasing amount of structural information available on natural OCs, development of appropriate allosteric models is foreseen to provide plausible molecular mechanisms for their complex functional performance. This may also have implications in the design of artificial olfaction systems.

  6. Hot spot analysis of nursing journals of statistic source published in 2010-2014 based on co-word analysis%基于共词分析的护理学统计源期刊2010-2014年研究热点分析

    Institute of Scientific and Technical Information of China (English)

    位珍珍; 张显珍; 张淑萍; 段红梅

    2015-01-01

    Objective To explore the articles sources coming form nursing journals of statistic source published in 2010-2014, to analyze research hot spot and explore national research and clinical practice hot spots of nursing field. Methods We selected Wanfang Database as data source to retrieve articles form 12 statistical source of nursing core journal, and utilized self-compiled computer program to count the frequency of key words and construct high frequency key words matrix, and then the SPSS 18. 0 software was used for cluster analysis. Results The results of research presented that there were 8 research hot spots of nursing core journals in 5 years including scale, psychological nursing, nursing education, improving nursing quality, application of evidence based nursing on critical patients, child perioperative nursing, rehabilitation nursing of apoplexy patients and chronic disease patient′s nursing. Conclusions The research hot spot of nursing core journals′articles reflect the key point work on clinical nursing and teaching and research of nursing field, and research hot spots of nursing core journals in 5 years can summarize as scale, psychological nursing, nursing education, improving nursing quality and so on 8 research topics.%目的:探讨以护理学统计源期刊论文为来源,分析2010—2014年论文的研究热点,探索我国护理领域的科学研究和临床实践热点。方法2015年8—9月以万方数据库为数据源,检索发表时间在2010—2014年的12种统计源护理学类科技期刊论文。应用自编计算机程序统计关键词词频,构建高频词矩阵,进一步应用SPSS 18.0软件进行聚类分析。结果研究结果显示,2010—2014年护理学统计源期刊的研究热点主要为8大主题,包括量表、心理护理、护理教育、提升护理质量、循证护理在重症患者中应用、儿童围术期护理、卒中患者康复护理、慢性病患者护理的相关研究。结论护理学统计源期

  7. Allosteric Regulation by a Critical Membrane

    CERN Document Server

    Kimchi, Ofer; Machta, Benjamin B

    2016-01-01

    Many of the processes that underly neural computation are carried out by ion channels embedded in the plasma membrane, a two-dimensional liquid that surrounds all cells. Recent experiments have demonstrated that this membrane is poised close to a liquid-liquid critical point in the Ising universality class. Here we use both exact and stochastic techniques on the lattice Ising model to explore the ramifications of proximity to criticality for proteins that are allosterically coupled to Ising composition modes. Owing to diverging generalized susceptibilities, such a protein's activity becomes strongly influenced by perturbations that influence the two relevant parameters of the critical point, especially the critical temperature. In addition, the protein's kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics.

  8. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter;

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects......(A) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  9. Untangling the glutamate dehydrogenase allosteric nightmare.

    Science.gov (United States)

    Smith, Thomas J; Stanley, Charles A

    2008-11-01

    Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.

  10. A unified framework and an alternative mechanism for allosteric regulation

    CERN Document Server

    Xing, J

    2007-01-01

    Allosteric regulation is an important property for many proteins. Several models have been proposed to explain the allosteric effect, such as the concerted MWC (Monod, Wyman, Changeux) model, the sequential KNF (Koshland, Nemethy, Filmer) model, and recent population shift models. Here we discuss a unified theoretical framework to describe allosteric effects. The existing models appear as special cases of the framework. The theoretical work also reveals an alternative mechanism currently overlooked. Theoretically it is possible that the reactivity of a protein is limited by some internal conformational change step (due to slow effective diffusion along rugged potential surfaces). Effector binding may modify the ruggedness and thus the protein dynamics and reactivity. Compared to conventional models, the new mechanism has less requirements on the mechanical properties of an allosteric protein to propagate mechanical signals over long distances. Thus some signal transduction proteins may adopt the new mechanism...

  11. Pathways of allosteric regulation in Hsp70 chaperones

    OpenAIRE

    Kityk, Roman; Vogel, Markus; Schlecht, Rainer; Bukau, Bernd; Mayer, Matthias P

    2015-01-01

    Central to the protein folding activity of Hsp70 chaperones is their ability to interact with protein substrates in an ATP-controlled manner, which relies on allosteric regulation between their nucleotide-binding (NBD) and substrate-binding domains (SBD). Here we dissect this mechanism by analysing mutant variants of the Escherichia coli Hsp70 DnaK blocked at distinct steps of allosteric communication. We show that the SBD inhibits ATPase activity by interacting with the NBD through a highly ...

  12. Rocky Mountain spotted fever

    Science.gov (United States)

    ... Mountain spotted fever is caused by the bacteria Rickettsia rickettsii (R. Rickettsii) , which is carried by ticks. ... Saunders; 2014:chap 212. Walker DH, Blaton LS. Rickettsia rickettsii and other spotted fever group rickettsiae (Rocky ...

  13. Allosteric modulators of the hERG K(+) channel: radioligand binding assays reveal allosteric characteristics of dofetilide analogs.

    Science.gov (United States)

    Yu, Zhiyi; Klaasse, Elisabeth; Heitman, Laura H; Ijzerman, Adriaan P

    2014-01-01

    Drugs that block the cardiac K(+) channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K(+) channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [(3)H]astemizole and [(3)H]dofetilide to the hERG K(+) channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC50 values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC50 values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K(+) channel, which is discussed in the light of findings on other ion channels. PMID:24200993

  14. Information visualization analysis of the research and hot spots in the early diagnosis of Alzheimer's disease 1992~2011%阿尔茨海默病早期诊断研究及其热点可视化分析1992~2011

    Institute of Scientific and Technical Information of China (English)

    龚佳剑; 刘玉婷

    2012-01-01

    A literature search was made on early diagnosis of Alzheimer's Disease at SC-EXPANDED, and 3 453 articles were retrieved. Based on bibliometric statistics, the word co-occurrence of social network analysis methods, using tools of bibexcel, Ucinet, Vosviewer, visual analysis of the literature in the field of time, countries, research institutions, authors, journals, and hot spots was performed.%选取SCI-EXPANDED数据库,检索阿尔茨海默病早期诊断方面的文献3 453条,基于文献计量统计,词共现、社会网络等分析方法,运用Bibexcel、Hiscite、Ucinet、Citespace、Vosviewer等工具,对阿尔茨海默病早期诊断文献发表的时间、国别、研究机构、作者、期刊及其研究热点等进行分析.

  15. Allosteric Inhibition of Human Immunodeficiency Virus Integrase

    Science.gov (United States)

    Gupta, Kushol; Brady, Troy; Dyer, Benjamin M.; Malani, Nirav; Hwang, Young; Male, Frances; Nolte, Robert T.; Wang, Liping; Velthuisen, Emile; Jeffrey, Jerry; Van Duyne, Gregory D.; Bushman, Frederic D.

    2014-01-01

    HIV-1 replication in the presence of antiviral agents results in evolution of drug-resistant variants, motivating the search for additional drug classes. Here we report studies of GSK1264, which was identified as a compound that disrupts the interaction between HIV-1 integrase (IN) and the cellular factor lens epithelium-derived growth factor (LEDGF)/p75. GSK1264 displayed potent antiviral activity and was found to bind at the site occupied by LEDGF/p75 on IN by x-ray crystallography. Assays of HIV replication in the presence of GSK1264 showed only modest inhibition of the early infection steps and little effect on integration targeting, which is guided by the LEDGF/p75·IN interaction. In contrast, inhibition of late replication steps was more potent. Particle production was normal, but particles showed reduced infectivity. GSK1264 promoted aggregation of IN and preformed LEDGF/p75·IN complexes, suggesting a mechanism of inhibition. LEDGF/p75 was not displaced from IN during aggregation, indicating trapping of LEDGF/p75 in aggregates. Aggregation assays with truncated IN variants revealed that a construct with catalytic and C-terminal domains of IN only formed an open polymer associated with efficient drug-induced aggregation. These data suggest that the allosteric inhibitors of IN are promising antiviral agents and provide new information on their mechanism of action. PMID:24904063

  16. Adenine nucleotides as allosteric effectors of pea seed glutamine synthetase.

    Science.gov (United States)

    Knight, T J; Langston-Unkefer, P J

    1988-08-15

    The effects of adenine nucleotides on pea seed glutamine synthetase (EC 6.3.1.2) activity were examined as a part of our investigation of the regulation of this octameric plant enzyme. Saturation curves for glutamine synthetase activity versus ATP with ADP as the changing fixed inhibitor were not hyperbolic; greater apparent Vmax values were observed in the presence of added ADP than the Vmax observed in the absence of ADP. Hill plots of data with ADP present curved upward and crossed the plot with no added ADP. The stoichiometry of adenine nucleotide binding to glutamine synthetase was examined. Two molecules of [gamma-32P]ATP were bound per subunit in the presence of methionine sulfoximine. These ATP molecules were bound at an allosteric site and at the active site. One molecule of either [gamma-32P]ATP or [14C]ADP bound per subunit in the absence of methionine sulfoximine; this nucleotide was bound at an allosteric site. ADP and ATP compete for binding at the allosteric site, although ADP was preferred. ADP binding to the allosteric site proceeded in two kinetic phases. A Vmax value of 1.55 units/mg was measured for glutamine synthetase with one ADP tightly bound per enzyme subunit; a Vmax value of 0.8 unit/mg was measured for enzyme with no adenine nucleotide bound at the allosteric site. The enzyme activation caused by the binding of ADP to the allosteric sites was preceded by a lag phase, the length of which was dependent on the ADP concentration. Enzyme incubated in 10 mM ADP bound approximately 4 mol of ADP/mol of native enzyme before activation was observed; the activation was complete when 7-8 mol of ADP were bound per mol of the octameric, native enzyme. The Km for ATP (2 mM) was not changed by ADP binding to the allosteric sites. ADP was a simple competitive inhibitor (Ki = 0.05 mM) of ATP for glutamine synthetase with eight molecules of ADP tightly bound to the allosteric sites of the octamer. Binding of ATP to the allosteric sites led to marked

  17. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.

    Science.gov (United States)

    Menniti, Frank S; Lindsley, Craig W; Conn, P Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A

    2013-01-01

    Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved.

  18. Binding leverage as a molecular basis for allosteric regulation.

    Directory of Open Access Journals (Sweden)

    Simon Mitternacht

    2011-09-01

    Full Text Available Allosteric regulation involves conformational transitions or fluctuations between a few closely related states, caused by the binding of effector molecules. We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein. We use Monte Carlo simulations to generate potential binding sites and either normal modes or pairs of crystal structures to describe relevant motions. We analyze single catalytic domains and multimeric allosteric enzymes with complex regulation. For the majority of the analyzed proteins, we find that both catalytic and allosteric sites have high binding leverage. Furthermore, our analysis of the catabolite activator protein, which is allosteric without conformational change, shows that its regulation involves other types of motion than those modulated at sites with high binding leverage. Our results point to the importance of incorporating dynamic information when predicting functional sites. Because it is possible to calculate binding leverage from a single crystal structure it can be used for characterizing proteins of unknown function and predicting latent allosteric sites in any protein, with implications for drug design.

  19. Study on the Model for Regulation of the Allosteric Enzyme Activity

    Institute of Scientific and Technical Information of China (English)

    LI,Qian-Zhong(李前忠); LUO,Liao-Fu(罗辽复); ZHANG,Li-Rong(张利绒)

    2002-01-01

    The effects of activator molecule and repressive molecule on binding process between allosteric enzyme and substrate are disused by considering the heterotropic effect of the regulating molecule that binds to allosteric enzyme. A model of allosteric enzyme with heterotropic effect is presented. The cooperativity and anticooperativity in the regulation process are studied.

  20. Pathways of allosteric regulation in Hsp70 chaperones.

    Science.gov (United States)

    Kityk, Roman; Vogel, Markus; Schlecht, Rainer; Bukau, Bernd; Mayer, Matthias P

    2015-01-01

    Central to the protein folding activity of Hsp70 chaperones is their ability to interact with protein substrates in an ATP-controlled manner, which relies on allosteric regulation between their nucleotide-binding (NBD) and substrate-binding domains (SBD). Here we dissect this mechanism by analysing mutant variants of the Escherichia coli Hsp70 DnaK blocked at distinct steps of allosteric communication. We show that the SBD inhibits ATPase activity by interacting with the NBD through a highly conserved hydrogen bond network, and define the signal transduction pathway that allows bound substrates to trigger ATP hydrolysis. We identify variants deficient in only one direction of allosteric control and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis. These findings provide evidence of an unexpected dichotomic allostery mechanism in Hsp70 chaperones and provide the basis for a comprehensive mechanical model of allostery in Hsp70s. PMID:26383706

  1. Talking on Current Situation and Selection of Strategies of Tourist Scenic Spot's Channel Managenent-Taking Mingyueshan&Hot Spring Scenic Spot as an Exanple%浅析旅游景区渠道管理的现状及策略选择——以明月山温泉风景名胜区为例

    Institute of Scientific and Technical Information of China (English)

    彭礴; 舒莉芬

    2011-01-01

    It's necessary to build sales channel that can make target customers knowing and buying the products of tourist scenic spot. However, the project of the channel management of the scenic spot was just carded out in many places, and it is in the exploratory stage, So, it's important for scenic spot marketing that how to build a scientific and effective sales channel. Intangibility of tourism products inevitably makes the difference of tourism products circulation fi'om physical products circulation, for the reason that we can't simply copy the theory and experience of physical products distribution. This paper will probe current situation and strategies of channel management of the scenic spot by learning the experience of Mingyueshan&Hot Spring Scenic spot's channel managements.%旅游景区产品要被目标顾客所接受和购买,渠道建设是必不可少的。然而,在许多地方景区渠道建设工作还刚刚起步,处在摸索阶段,如何构建一条科学有效的销售渠道,成为景区营销工作的一个重要内容。旅游产品的无形性,必然使得旅游产品流通与实体产品流通不同,在构建渠道过程中,这一特性应该体现出来,因而,简单照搬实体产品分销的理论和经验是不够的。借助对明月山温泉风景名胜区渠道工作的经验,本文探讨景区渠道管理的现状及策略的选择。

  2. Dark spots along slowly scaling chains of plasmonic nanoparticles

    CERN Document Server

    Zito, Gianluigi; Sasso, Antonio

    2016-01-01

    We numerically investigate the optical response of slowly scaling linear chains of mismatched silver nanoparticles. Hybridized plasmon chain resonances manifest unusual local field distributions around the nanoparticles that result from symmetry breaking of the geometry. Importantly, we find localization patterns characterized by bright hot-spots alternated by what we term \\textit{dark} spots. A dark spot is associated to dark plasmons that have collinear and antiparallel dipole moments along the chain. As a result, the field amplification in the dark interjunction gap is extinguished for incident polarization parallel to the chain axis. Despite the strong plasmonic coupling, the nanoparticles on the sides of this dark gap experience a dramatic asymmetric field amplification with amplitude gain contrast $> 2 \\times 10^2$. Remarkably, also for polarization orthogonal to the axis, gap hot-spots form on resonance.

  3. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2006-01-01

    Conventionally, an allosteric modulator is neutral in respect of efficacy and binds to a receptor site distant from the orthosteric site of the endogenous agonist. However, recently compounds being ago-allosteric modulators have been described i.e., compounds acting both as agonists on their own...... influence the potency of the endogenous agonist. It is of interest that at least some endogenous agonists can only occupy one protomer of a dimeric 7TM receptor complex at a time and thereby they leave the orthosteric binding site in the allosteric protomer free, potentially for binding of exogenous......, allosteric modulators. If the allosteric modulator is an agonist, it is an ago-allosteric modulator; if it is neutral, it is a classical enhancer. Molecular mapping in hetero-dimeric class-C receptors, where the endogenous agonist clearly binds only in one protomer, supports the notion that allosteric...

  4. HOT 2012

    DEFF Research Database (Denmark)

    Lund, Henriette Romme

    Undersøgelse af, hvad der er hot - og hvad der burde være hot på læseområdet med 21 læsekyndige. Undersøgelsen er gennemført siden 2010. HOT-undersøgelsen er foretaget af Nationalt Videncenter for Læsning - Professionshøjskolerne i samarb. med Dansklærerforeningen...

  5. An allosteric inhibitor of protein arginine methyltransferase 3.

    Science.gov (United States)

    Siarheyeva, Alena; Senisterra, Guillermo; Allali-Hassani, Abdellah; Dong, Aiping; Dobrovetsky, Elena; Wasney, Gregory A; Chau, Irene; Marcellus, Richard; Hajian, Taraneh; Liu, Feng; Korboukh, Ilia; Smil, David; Bolshan, Yuri; Min, Jinrong; Wu, Hong; Zeng, Hong; Loppnau, Peter; Poda, Gennadiy; Griffin, Carly; Aman, Ahmed; Brown, Peter J; Jin, Jian; Al-Awar, Rima; Arrowsmith, Cheryl H; Schapira, Matthieu; Vedadi, Masoud

    2012-08-01

    PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro. Here, we report the identification of a PRMT3 inhibitor (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(2-cyclohexenylethyl)urea; compound 1) with IC50 value of 2.5 μM by screening a library of 16,000 compounds using H4 (1-24) peptide as a substrate. The crystal structure of PRMT3 in complex with compound 1 as well as kinetic analysis reveals an allosteric mechanism of inhibition. Mutating PRMT3 residues within the allosteric site or using compound 1 analogs that disrupt interactions with allosteric site residues both abrogated binding and inhibitory activity. These data demonstrate an allosteric mechanism for inhibition of protein arginine methyltransferases, an emerging class of therapeutic targets.

  6. The structure and allosteric regulation of glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2011-09-01

    Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the chemical mechanism for GDH has remained unchanged through epochs of evolution, it was not clear how or why animals needed to evolve such a finely tuned form of this enzyme. As reviewed here, recent studies have begun to elucidate these issues. Allosteric regulation first appears in the Ciliates and may have arisen to accommodate evolutionary changes in organelle function. The occurrence of allosteric regulation appears to be coincident with the formation of an 'antenna' like feature rising off the tops of the subunits that may be necessary to facilitate regulation. In animals, this regulation further evolved as GDH became integrated into a number of other regulatory pathways. In particular, mutations in GDH that abrogate GTP inhibition result in dangerously high serum levels of insulin and ammonium. Therefore, allosteric regulation of GDH plays an important role in insulin homeostasis. Finally, several compounds have been identified that block GDH-mediated insulin secretion that may be to not only find use in treating these insulin disorders but to kill tumors that require glutamine metabolism for cellular energy.

  7. Experimental study of bulk storage ignition by hot points

    OpenAIRE

    Janes, Agnès; Carson, Douglas

    2013-01-01

    International audience An experimental study of ignition risk due to hot points in the storage of bulk materials is required to ensure fire safety. Many parameters are involved in this phenomenon: nature of the material, storage volume and temperature, type and size of hot point, etc. The aim of this study is to determine critical ignition temperatures of hot spots embedded in powder materials for different conditions and with several types of hot points. Materials selected for this study ...

  8. Evidence of a short-range incommensurate d-wave charge order from a fermionic two-loop renormalization group calculation of a 2D model with hot spots

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Vanuildo S de [Instituto de Física, Universidade Federal de Goiás, 74.001-970, Goiânia-GO (Brazil); Freire, Hermann, E-mail: hfreire@mit.edu [Instituto de Física, Universidade Federal de Goiás, 74.001-970, Goiânia-GO (Brazil); Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 2139 (United States)

    2014-09-15

    The two-loop renormalization group (RG) calculation is considerably extended here for the two-dimensional (2D) fermionic effective field theory model, which includes only the so-called “hot spots” that are connected by the spin-density-wave (SDW) ordering wavevector on a Fermi surface generated by the 2D t−t{sup ′} Hubbard model at low hole doping. We compute the Callan–Symanzik RG equation up to two loops describing the flow of the single-particle Green’s function, the corresponding spectral function, the Fermi velocity, and some of the most important order-parameter susceptibilities in the model at lower energies. As a result, we establish that–in addition to clearly dominant SDW correlations–an approximate (pseudospin) symmetry relating a short-range incommensurated-wave charge order to the d-wave superconducting order indeed emerges at lower energy scales, which is in agreement with recent works available in the literature addressing the 2D spin-fermion model. We derive implications of this possible electronic phase in the ongoing attempt to describe the phenomenology of the pseudogap regime in underdoped cuprates.

  9. Extracellular loop 2 of the free Fatty Acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator

    DEFF Research Database (Denmark)

    Smith, Nicola J; Ward, Richard J; Stoddart, Leigh A;

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molec...

  10. Hot Groups.

    Science.gov (United States)

    Vail, Kathleen

    1996-01-01

    Collaborators sparked by creative ideas and obsessed by a common task may not realize they're part of a "hot group"--a term coined by business professors Harold J. Leavitt and Jean Lipman-Blumen. Spawned by group decision making and employee empowerment, hot groups can flourish in education settings. They're typically small, short lived, and goal…

  11. Western Cultural and Creative Industry Research:Academic Community and Hot-spot Evolution%西方文化创意产业研究院学术群体与热点演进

    Institute of Scientific and Technical Information of China (English)

    马仁锋; 梁贤军; 姜炎鹏

    2015-01-01

    采用www.isiknowledge.com数据库收录的2001年~2013年期间2431篇文化创意产业相关文献,利用Citespace、Histcite两软件进行文献引用关系和知识图谱的可视化处理,分析热点文献的研究机构与研究领域,解读西方文化创意产业研究热点演进趋势。研究发现:①西方文化创意产业研究学术群体主要集中在澳大利亚、英国与美国,具体而言澳大利亚以昆士兰科技大学、昆士兰大学、麦考瑞大学、悉尼科技大学的艺术、设计与传媒为阵营的文化创意产业研究和以伍伦贡大学的文化地理学与城市文化经济等领域研究阵营,而英国则以利兹大学、格拉斯哥大学为首的艺术、设计、传媒和文化地理学二元并进的研究阵营,南加利亚福尼亚大学为代表的美国影视文化研究阵营;②文化创意产业研究力量与地方创意经济技发展水平存在两种匹配类型:澳大利亚呈协调发展,而美国、英国的文化创意产业研究机构与地方创意经济发展水平存在空间错位;③西方文化创意产业研究的高频作者是Chris Gibson、Jason Potts、Stuart Cunningham、Terry Flew,但单篇文献被引率最高的则是Florida R L、Caves R E、Scott A J、Hesmondhalgh D、Pratt AC;④文化创意产业研究热点是创意力、创意集群、创意阶层、创意城市、创意网络、国家创意产业政策等,且形成以Richard Florida为核心创意阶层理论派;以Charles Landry为核心创意城市假说派;以John Howkins、Stuart Cunningham等为核心的艺术、设计、媒介及其商业价值衍生派。%In order to explore the trend and hot issues objectively, a database has been set up from the source of www.isiknowledge.com with its 2431 papers about cultural and creative industry from 2001 to 2013.The institutes, country and cited reference citation relationship are visualized on the Cites-pace II and Histcite platform

  12. Spotted Seal Distribution Map

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains GIS layers that depict the known spatial distributions (i.e., ranges) and reported breeding areas of spotted seals (Phoca largha). It was...

  13. Mononucleosis spot test

    Science.gov (United States)

    Monospot test; Heterophile antibody test; Heterophile agglutination test; Paul-Bunnell test; Forssman antibody test ... The mononucleosis spot test is done when symptoms of mononucleosis are ... Fatigue Fever Large spleen (possibly) Sore throat Tender ...

  14. 北京地区耳聋残疾人群大前庭水管相关SLC26A4基因热点突变分子流行病学调查%Epidemiological investigation of SLC26A4 gene hot-spot mutation in patients with enlarged vestibular aqueduct among deaf population in Beijing

    Institute of Scientific and Technical Information of China (English)

    左路杰; 张勋; 袁永一; 王国建; 康东洋; 张昕; 戴朴

    2012-01-01

    Objective To study frequency of SLC26A4 genes hot-spot mutations IVS7-2 A>G and 2168A>G among deaf people in Beijing, to determine its value in molecular diagnosis among people with deafness. Mothods The study involved 6247 subjects in Beijing area with disability cards showing deafness-related disability. The genomic DNA sample was extracted from peripheral blood .The deafness SLC26A4 gene mutations of IVS7-2A>G and 2168A>G were distinguished by a gene test chip from CaptalBio Corporation and their frequencies analyzed. Results Among these hearing disabled people in Beijing, 177 carried SLC26A4 IVS7-2 A>G and 2168 A>G mutations, yielding a positive detection rate of 2.83% (177/6247) and a diagnosis rate of 0.46% (41/6247). There were 141 SLC26A4 IVS7-2 A>G mutations carriers (27 homozygous mutation cases and 114 heterozygous mutation cases), 26 SLC26A4 2168 A>G mutations carriers (4 homozygous mutation cases and 22 heterozygous mutation cases) and 10 SLC26A4 2168A>G/IVS7~2A>G compound heterozygous mutation carriers. In 97.17% (6070/6247) of these hearing disabled persons SLC26A4 gene hot-spot mutations were not detected. Conclusions 1 , Molecular diagnosis was established in 0.46% (41/6247) of this population of hearing disabled persons through testing SLC26A4 gene mutations IVS7-2 A>G and 2168 A>G. 2,The rate of SLC26A4 gene hot-spot mutations in Beijing area appears to be lower than among patients seen in our clinic. The study helps increase our understanding of the distribution of SLC26A4 gene hot-spot mutations in relation to enlarged vestibular aqueduct syndrome among hearing disabled people in Beijing area, improve diagnosis among hearing disabled people at the molecular level, and provide guidance in counseling patients with positive IVS7-2 A>G and 2168 A>G mutations in marriage and reproduction..%目的 分析北京耳聋残疾人群中SLC26A4基因热点突变IVS7-2A>G和2168A>G发生频率,初步探讨SLC26A4基因热点突变在北京地区耳聋

  15. 基于国际专利分类法的上海中药产业创新技术热点分析%Analysis on Hot Spots of Innovative Technology of Chinese Medicine Industry in Shanghai Based on The IPC Classification of Patents

    Institute of Scientific and Technical Information of China (English)

    张洋

    2015-01-01

    Objective To analysis the hot spots of innovative technology of Chinese medicine industry in Shanghai during the recent years.Methods Patent Database of State Intelletual Property Office was retrieved by IPC class numbers combined with keywords and the IPC classification of the Chinese medicine patents in Shanghai area during 2002-2013 were under statistical analysis.Results The hot spot distribution of therapeutic activity of TCM preparations:Antineoplastic is the most important activity of Chinese medicine development, followed by the activities of treatment of inadequate blood flow or cardiovascular system diseases, such as hyperglycemia, high cholesterol, and so on. The activity of treatment of the digestive tract or digestive system diseases, followed by the activities of anti infection, antiviral, antibacterial, anti-inflammatory treatment, etc. The hot spot distribution of dosage:Researches on new dosage of Chinese medicine were mainly reflected in the improvement of traditional dosage form and development of new formulations. The capsules, tablets, oral liquid, and injections were the new dosage forms under the most researches. The distribution of medical resources:Medicinal plants or animals mainly came from “angiosperm”. Medicinal animals were less than medicinal plants, which mainly belonged to insecta.ConclusionThe hot spots of innovative technology of Chinese medicine industry in Shanghai are mainly distributed in the medicine of anti-tumor, cardiocerebral vascular diseases, digestive system diseases and so on in recent years. The researches of new formulation focus on the traditional dosage form improvement and new formulations development. “Angiosperm” is the key to the development of medicinal plants.%目的:分析近年来我国上海地区中药产业创新技术研究热点。方法采用国际专利分类法(IPC)分类号结合关键词组合检索《国家知识产权局专利数据库》,对2002-2013年

  16. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    CERN Document Server

    Amor, Benjamin R C; Yaliraki, Sophia N; Barahona, Mauricio

    2016-01-01

    Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of...

  17. VISUALIZATION ANALYSIS OF THEORY BASE AND RESEARCH HOT SPOTS OF DOMESTIC AND INTERNATIONAL ECOLOGICAL COMPENSATION%国内外生态补偿基础理论与研究热点的可视化分析

    Institute of Scientific and Technical Information of China (English)

    胡小飞; 傅春; 陈伏生; 廖志娟

    2012-01-01

    With the aggravation of the ecological and environmental problems faced by humanity,the ecological compensation has become a hot topic of widespread concerns amongst domestic and foreign scholars.In order to understand the advances of ecological compensation,we carries out statistical analysis about the time of its publication based on 929documents from Web of Science and the Chinese Social Science Citation Index(CSSCI) database on the subject of ecology compensation in the time period of 1998-2011,and analyzes co-citation of literary documents and keyword co-occurrence using the CiteSpace Ⅱ software.Meanwhile,the key scholarly documents are listed,and research topics of eco-compensation are briefly concluded using knowledge mapping visual tool.We found the number of ecological compensation paper presented the trend of fluctuation growth from 1998to 2011.Research on eco-compensation of carbon sinks and REDD in the context of global climate change,eco-compensation zones and evaluation on the implementation of ecological compensation,strengthening the ecological compensation standards of the wetlands,nature reserves,watersheds and other ecosystem,application of computer management software(such as GIS,SWAT,InVEST) would become the focus issues in the future research on eco-compensation.Our results also showed that the domestic scholars had made great progress in the theory of eco-compensation,and the practice researches in forests,watersheds,nature reserves and other areas were strengthened in recent years.%随着人类面临的生态环境问题加重,生态补偿已成为国内外学者广泛关注的热点问题。为清晰地了解国内外生态补偿的研究现状和未来发展,以Web of Science、中文社会科学引文索引(CSSCI)数据库中1998~2011年有关生态补偿的929篇文献为基础,应用CiteSpace Ⅱ软件分析了论文发表数量、文献共被引和关键词共现等特征,并以知识图谱可视化的方式,归纳了近年来

  18. PPR Great Red Spot Temperature Map

    Science.gov (United States)

    1996-01-01

    This map shows temperature for the region around Jupiter's Great Red Spot and an area to the northwest. It corresponds to a level in Jupiter's atmosphere where the pressure is 1/2 of the of the Earth's at sea level (500 millibars), the same as it is near 6000 meters (20,000 feet) above sea level on Earth. The center of Great Red Spot appears colder than the surrounding areas, where air from below is being brought up. The 'panhandle' to the northwest is warmer and drier, and the gases there are descending, so it is much clearer of clouds. Compare this map to one released earlier at a higher place in the atmosphere (250 millibars or 12000 meters). The center of the Great Red Spot is warmer lower in the atmosphere, and a white 'hot spot' appears in this image that is not present at the higher place. This map was made from data taken by the Photopolarimeter/Radiometer (PPR) instrument on June 26, 1996.Launched in October 1989, Galileo entered orbit around Jupiter on December 7, 1995. The spacecraft's mission is to conduct detailed studies of the giant planet, its largest moons and the Jovian magnetic environment.JPL manages the Galileo mission for NASA's Office of Space Science, Washington, D.C.This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  19. An allosteric photoredox catalyst inspired by photosynthetic machinery.

    Science.gov (United States)

    Lifschitz, Alejo M; Young, Ryan M; Mendez-Arroyo, Jose; Stern, Charlotte L; McGuirk, C Michael; Wasielewski, Michael R; Mirkin, Chad A

    2015-03-30

    Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.

  20. The Allosteric Switching Mechanism in Bacteriophage MS2

    CERN Document Server

    Perkett, Matthew R

    2015-01-01

    In this article we use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopt different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We disc...

  1. Allosteric Pathways in the PPARγ-RXRα nuclear receptor complex

    Science.gov (United States)

    Ricci, Clarisse G.; Silveira, Rodrigo L.; Rivalta, Ivan; Batista, Victor S.; Skaf, Munir S.

    2016-01-01

    Understanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Ω-loops and PPARγ-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors.

  2. Light-activated DNA binding in a designed allosteric protein

    Energy Technology Data Exchange (ETDEWEB)

    Strickland, Devin; Moffat, Keith; Sosnick, Tobin R. (UC)

    2008-09-03

    An understanding of how allostery, the conformational coupling of distant functional sites, arises in highly evolvable systems is of considerable interest in areas ranging from cell biology to protein design and signaling networks. We reasoned that the rigidity and defined geometry of an {alpha}-helical domain linker would make it effective as a conduit for allosteric signals. To test this idea, we rationally designed 12 fusions between the naturally photoactive LOV2 domain from Avena sativa phototropin 1 and the Escherichia coli trp repressor. When illuminated, one of the fusions selectively binds operator DNA and protects it from nuclease digestion. The ready success of our rational design strategy suggests that the helical 'allosteric lever arm' is a general scheme for coupling the function of two proteins.

  3. Allosteric process of human glucokinase conducive to fight against diabetes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ More than 200 million people worldwide have diabetes. In China alone, about 60 million people are suffering from the disease.Fortunately, scientists are pushing back its boundaries. For instance, a recent study by CAS researchers may shed new light on the treatment of the disease by making cutting-edge progress on studies of the allosteric process of human glucokinase, which has been published by the latest issue of the Proceedings of National Academy of Sciences.

  4. Divergent allosteric patterns verify the regulatory paradigm for aspartate transcarbamylase.

    Science.gov (United States)

    Wales, M E; Madison, L L; Glaser, S S; Wild, J R

    1999-12-17

    The native Escherichia coli aspartate transcarbamoylase (ATCase, E.C. 2.1.3.2) provides a classic allosteric model for the feedback inhibition of a biosynthetic pathway by its end products. Both E. coli and Erwinia herbicola possess ATCase holoenzymes which are dodecameric (2(c3):3(r2)) with 311 amino acid residues per catalytic monomer and 153 and 154 amino acid residues per regulatory (r) monomer, respectively. While the quaternary structures of the two enzymes are identical, the primary amino acid sequences have diverged by 14 % in the catalytic polypeptide and 20 % in the regulatory polypeptide. The amino acids proposed to be directly involved in the active site and nucleotide binding site are strictly conserved between the two enzymes; nonetheless, the two enzymes differ in their catalytic and regulatory characteristics. The E. coli enzyme has sigmoidal substrate binding with activation by ATP, and inhibition by CTP, while the E. herbicola enzyme has apparent first order kinetics at low substrate concentrations in the absence of allosteric ligands, no ATP activation and only slight CTP inhibition. In an apparently important and highly conserved characteristic, CTP and UTP impose strong synergistic inhibition on both enzymes. The co-operative binding of aspartate in the E. coli enzyme is correlated with a T-to-R conformational transition which appears to be greatly reduced in the E. herbicola enzyme, although the addition of inhibitory heterotropic ligands (CTP or CTP+UTP) re-establishes co-operative saturation kinetics. Hybrid holoenzymes assembled in vivo with catalytic subunits from E. herbicola and regulatory subunits from E. coli mimick the allosteric response of the native E. coli holoenzyme and exhibit ATP activation. The reverse hybrid, regulatory subunits from E. herbicola and catalytic subunits from E. coli, exhibited no response to ATP. The conserved structure and diverged functional characteristics of the E. herbicola enzyme provides an opportunity

  5. The structural basis of ATP as an allosteric modulator.

    OpenAIRE

    Shaoyong Lu; Wenkang Huang; Qi Wang; Qiancheng Shen; Shuai Li; Ruth Nussinov; Jian Zhang

    2014-01-01

    Adenosine-5'-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP...

  6. The Structural Basis of ATP as an Allosteric Modulator

    OpenAIRE

    Lu, Shaoyong; Huang, Wenkang; Wang, Qi; Shen, Qiancheng; Li, Shuai; Nussinov, Ruth; Zhang, Jian

    2014-01-01

    Adenosine-5’-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP...

  7. Allosteric indicator displacement enzyme assay for a cyanogenic glycoside.

    Science.gov (United States)

    Jose, D Amilan; Elstner, Martin; Schiller, Alexander

    2013-10-18

    Indicator displacement assays (IDAs) represent an elegant approach in supramolecular analytical chemistry. Herein, we report a chemical biosensor for the selective detection of the cyanogenic glycoside amygdalin in aqueous solution. The hybrid sensor consists of the enzyme β-glucosidase and a boronic acid appended viologen together with a fluorescent reporter dye. β-Glucosidase degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and benzaldehyde. Only the released cyanide binds at the allosteric site of the receptor (boronic acid) thereby inducing changes in the affinity of a formerly bound fluorescent indicator dye at the other side of the receptor. Thus, the sensing probe performs as allosteric indicator displacement assay (AIDA) for cyanide in water. Interference studies with inorganic anions and glucose revealed that cyanide is solely responsible for the change in the fluorescent signal. DFT calculations on a model compound revealed a 1:1 binding ratio of the boronic acid and cyanide ion. The fluorescent enzyme assay for β-glucosidase uses amygdalin as natural substrate and allows measuring Michaelis-Menten kinetics in microtiter plates. The allosteric indicator displacement assay (AIDA) probe can also be used to detect cyanide traces in commercial amygdalin samples. PMID:24123550

  8. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  9. Identification of the allosteric regulatory site of insulysin.

    Directory of Open Access Journals (Sweden)

    Nicholas Noinaj

    Full Text Available BACKGROUND: Insulin degrading enzyme (IDE is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. PRINCIPAL FINDINGS: The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  10. Computational approaches to detect allosteric pathways in transmembrane molecular machines.

    Science.gov (United States)

    Stolzenberg, Sebastian; Michino, Mayako; LeVine, Michael V; Weinstein, Harel; Shi, Lei

    2016-07-01

    Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID:26806157

  11. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Directory of Open Access Journals (Sweden)

    Francisco Andrés Peralta

    2016-07-01

    Full Text Available Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

  12. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  13. Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.

    Science.gov (United States)

    Kahsai, Alem W; Wisler, James W; Lee, Jungmin; Ahn, Seungkirl; Cahill Iii, Thomas J; Dennison, S Moses; Staus, Dean P; Thomsen, Alex R B; Anasti, Kara M; Pani, Biswaranjan; Wingler, Laura M; Desai, Hemant; Bompiani, Kristin M; Strachan, Ryan T; Qin, Xiaoxia; Alam, S Munir; Sullenger, Bruce A; Lefkowitz, Robert J

    2016-09-01

    G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms. Here, using a highly diverse RNA library combined with advanced selection strategies involving state-of-the-art next-generation sequencing and bioinformatics analyses, we identify RNA aptamers that bind a prototypical GPCR, the β2-adrenoceptor (β2AR). Using biochemical, pharmacological, and biophysical approaches, we demonstrate that these aptamers bind with nanomolar affinity at defined surfaces of the receptor, allosterically stabilizing active, inactive, and ligand-specific receptor conformations. The discovery of RNA aptamers as allosteric GPCR modulators significantly expands the diversity of ligands available to study the structural and functional regulation of GPCRs. PMID:27398998

  14. Glutamate dehydrogenase: structure, allosteric regulation, and role in insulin homeostasis.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2014-01-01

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine and inhibitors include GTP, palmitoyl CoA, and ATP. Spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds blocked the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  15. The structure and allosteric regulation of mammalian glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2012-03-15

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine, while the most important inhibitors include GTP, palmitoyl CoA, and ATP. Recently, spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds were found to block the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  16. Identification of the Allosteric Regulatory Site of Insulysin

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W.; Gerrard, Juliet Ann

    2011-06-24

    Background Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. Principal Findings The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Conclusions/Significance Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  17. Identification of the Allosteric Regulatory Site of Insulysin

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W. (U. Sao Paulo); (Kentucky)

    2012-05-25

    Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the A{beta} peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  18. Hot electron bolometer development at Chalmers University of Technology

    Science.gov (United States)

    Merkel, Harald F.; Cherednichenko, Sergey; Khosropanah, Pourya; Ottosson, Therese; Baubert, Jean; Kollberg, Erik L.

    2004-10-01

    In this paper recent developments of Hot Electron Bolometric receivers performed at Chalmers are summarized. This comprises progress on the mixers for HIFI and membrane HEB. All devices are modelled using Hot Spot model taking Andreev reflection at the interface between the normal conductor and the superconductor into account.

  19. SpotADAPT

    DEFF Research Database (Denmark)

    Kaulakiene, Dalia; Thomsen, Christian; Pedersen, Torben Bach;

    2015-01-01

    Having constantly increasing amounts of data, the analysis of it is often entrusted for a MapReduce framework. The execution of an analytical workload can be cheapened by adopting cloud computing resources, and in particular by using spot instances (cheap, fluctuating price instances) offered by ...

  20. Analysis of hot spots of clinical psychological nursing research based on frequency analysis and co word clustering in recent 5 years%基于词频分析和共词聚类的近5年临床心理护理研究热点分析

    Institute of Scientific and Technical Information of China (English)

    赵娇; 韩世范

    2016-01-01

    [目的]揭示国际临床心理护理研究热点及临床心理护理研究现状,为我国临床心理护理研究提供参考。[方法]选取2011年—2015年PubMed数据库临床心理护理相关文献作为研究对象,利用书目共现分析系统(Bi-comb 2.0软件)对主题词进行词频分析,利用 SPSS 22.0统计软件对主题词进行系统聚类,并用双聚类软件(gCLUTO)进行双聚类分析对系统聚类结果进行调整。[结果]系统聚类得到3组聚类效果较好的主题词,双聚类有3个类团聚类较好,另外1个类团聚类效果较差。通过对高频主题词进行聚类分析,总结出近5年临床心理护理的3个主要研究热点:家庭在临床心理护理过程中越来越重要,精神、心理障碍成为临床心理护理重点关注的问题,肿瘤病人成为临床心理护理需要重点关注的群体。[结论]基于词频分析和共词聚类的近5年临床心理护理研究热点分析有助于了解目前国际临床心理护理研究热点,对我国临床心理护理研究起到一定的借鉴作用。%Objective:In order to provide a reference for clinical psychological nursing research in China,it re-vealed the hot spots of international clinical psychological nursing research and the status quo of clinical psycho-logical nursing research.Methods:The clinical psychological nursing related literatures were selected as the re-search object in PubMed database from 2011 to 2015.The bibliographic co occurrence analysis system (Bicomb 2)was used for frequency analysis of subject words.SPSS 22.0 statistical software was used to cluster the sub-j ect headings,and the double cluster software (gCLUTO)was used to adj ust the clustering results.Results:The systematic clustering had been used to get the 3 groups of subj ect headings with better clustering effect,and the double cluster had 3 better classes,and one poor cluster.Through cluster analysis of high frequency subj ect headings

  1. The satellite-based remote sensing of particulate matter (PM) in support to urban air quality: PM variability and hot spots within the Cordoba city (Argentina) as revealed by the high-resolution MAIAC-algorithm retrievals applied to a ten-years dataset (2

    Science.gov (United States)

    Della Ceca, Lara Sofia; Carreras, Hebe A.; Lyapustin, Alexei I.; Barnaba, Francesca

    2016-04-01

    some areas of the city (hot spots). These hot spots were put in relation with changes in vehicular traffic flows after the construction of new roads in the urban area. The monthly-resolved analysis showed a marked seasonal cycle, evidencing the influence of both meteorological conditions and season-dependent sources on the AOD parameter. For instance, in the Cordoba rural area an increase of AOD is observed during March-April, which is the soybean harvesting period, the main agricultural activity in the region. Furthermore, higher AOD signals were observed in the vicinity of main roads during summer months (December to February), likely related to the increase in vehicular traffic flow due to tourism. Long-range transport is also shown to play a role at the city scale, as high AODs throughout the study area are observed between August and November. In fact, this is the biomass-burning season over the Amazon region and over most of South America, with huge amounts of fire-related particles injected into the atmosphere and transported across the continent [4]. References [1] WHO, 2013; REVIHAAP, Project Technical Report [2] Lyapustin et al., 2011; doi: 10.1029/2010JD014986 [3] Holben et al., 1998, doi:10.1016/S0034-4257(98)00031-5 [4] Castro et al., 2013; doi:10.1016/j.atmosres.2012.10.026

  2. Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N. [Hopital de la Salpetriere, Paris (France)] [and others

    1996-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.

  3. Formation of super-resolution spot through nonlinear Fabry-Perot cavity structures: theory and simulation.

    Science.gov (United States)

    Wei, Jingsong; Wang, Rui; Yan, Hui; Fan, Yongtao

    2014-04-01

    This study explores how interference manipulation breaks through the diffraction limit and induces super-resolution nano-optical hot spots through the nonlinear Fabry-Perot cavity structure. The theoretical analytical model is established, and the numerical simulation results show that when the thickness of the nonlinear thin film inside the nonlinear Fabry-Perot cavity structure is adjusted to centain value, the constructive interference effect can be formed in the central point of the spot, which causes the nanoscale optical hot spot in the central region to be produced. The simulation results also tell us that the hot spot size is sensitive to nonlinear thin film thickness, and the accuracy is required to be up to nanometer or even subnanometer scale, which is very large challenging for thin film deposition technique, however, slightly changing the incident laser power can compensate for drawbacks of low thickness accuracy of nonlinear thin films. Taking As(2)S(3) as the nonlinear thin film, the central hot spot with a size of 40nm is obtained at suitable nonlinear thin film thickness and incident laser power. The central hot spot size is only about λ/16, which is very useful in super-high density optical recording, nanolithography, and high-resolving optical surface imaging.

  4. Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors - A Structural Perspective of Ligands and Mutants

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Isberg, Vignir; Tehan, Benjamin G;

    2015-01-01

    The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far ......Glu allosteric modulator binding modes relates to selective pharmacological actions will be very valuable for rational design of safer drugs....

  5. Advances in NMR Methods To Map Allosteric Sites: From Models to Translation.

    Science.gov (United States)

    Boulton, Stephen; Melacini, Giuseppe

    2016-06-01

    The last five years have witnessed major developments in the understanding of the allosteric phenomenon, broadly defined as coupling between remote molecular sites. Such advances have been driven not only by new theoretical models and pharmacological applications of allostery, but also by progress in the experimental approaches designed to map allosteric sites and transitions. Among these techniques, NMR spectroscopy has played a major role given its unique near-atomic resolution and sensitivity to the dynamics that underlie allosteric couplings. Here, we highlight recent progress in the NMR methods tailored to investigate allostery with the goal of offering an overview of which NMR approaches are best suited for which allosterically relevant questions. The picture of the allosteric "NMR toolbox" is provided starting from one of the simplest models of allostery (i.e., the four-state thermodynamic cycle) and continuing to more complex multistate mechanisms. We also review how such an "NMR toolbox" has assisted the elucidation of the allosteric molecular basis for disease-related mutations and the discovery of novel leads for allosteric drugs. From this overview, it is clear that NMR plays a central role not only in experimentally validating transformative theories of allostery, but also in tapping the full translational potential of allosteric systems. PMID:27111288

  6. Sediment trapping by dams creates methane emission hot spots

    DEFF Research Database (Denmark)

    Maeck, A.; Delsontro, T.; McGinnis, Daniel F.;

    2013-01-01

    Inland waters transport and transform substantial amounts of carbon and account for similar to 18% of global methane emissions. Large reservoirs with higher areal methane release rates than natural waters contribute significantly to freshwater emissions. However, there are millions of small dams ...

  7. Traffic Engineering without Congestion Hot Spots in MPLS

    Directory of Open Access Journals (Sweden)

    A.Padmapriya,

    2010-10-01

    Full Text Available Traffic Engineering [1] broadly relates to optimization of the performance of the operational IP network. In networking, network congestion occurs when a link or node is carrying so much data that its quality of service deteriorates. Typical effects include queueing delay, packet loss or the blocking of new connections. A consequence of these latter two is that incremental increases in offered load lead either only to small increases in network throughput, or to an actual reduction in network throughput. This paper discusses methods like PNP approach [2] and HITS method for improving QoS [3], which are used for traffic engineering in MPLS. This paper will examine the two approaches; discuss solutions in both PNP approach and HITS method for improving QoS and point to topics for research and advanced development.

  8. Coral mucus is a hot spot for viral infections

    OpenAIRE

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-01-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are ...

  9. The Role of Viscosity in TATB Hot Spot Ignition

    Energy Technology Data Exchange (ETDEWEB)

    Fried, L E; Zepeda-Ruis, L; Howard, W M; Najjar, F; Reaugh, J E

    2011-08-02

    The role of dissipative effects, such as viscosity, in the ignition of high explosive pores is investigated using a coupled chemical, thermal, and hydrodynamic model. Chemical reactions are tracked with the Cheetah thermochemical code coupled to the ALE3D hydrodynamic code. We perform molecular dynamics simulations to determine the viscosity of liquid TATB. We also analyze shock wave experiments to obtain an estimate for the shock viscosity of TATB. Using the lower bound liquid-like viscosities, we find that the pore collapse is hydrodynamic in nature. Using the upper bound viscosity from shock wave experiments, we find that the pore collapse is closest to the viscous limit.

  10. Plant cell nucleolus as a hot spot for iron.

    Science.gov (United States)

    Roschzttardtz, Hannetz; Grillet, Louis; Isaure, Marie-Pierre; Conéjéro, Geneviève; Ortega, Richard; Curie, Catherine; Mari, Stéphane

    2011-08-12

    Many central metabolic processes require iron as a cofactor and take place in specific subcellular compartments such as the mitochondrion or the chloroplast. Proper iron allocation in the different organelles is thus critical to maintain cell function and integrity. To study the dynamics of iron distribution in plant cells, we have sought to identify the different intracellular iron pools by combining three complementary imaging approaches, histochemistry, micro particle-induced x-ray emission, and synchrotron radiation micro X-ray fluorescence. Pea (Pisum sativum) embryo was used as a model in this study because of its large cell size and high iron content. Histochemical staining with ferrocyanide and diaminobenzidine (Perls/diaminobenzidine) strongly labeled a unique structure in each cell, which co-labeled with the DNA fluorescent stain DAPI, thus corresponding to the nucleus. The unexpected presence of iron in the nucleus was confirmed by elemental imaging using micro particle-induced x-ray emission. X-ray fluorescence on cryo-sectioned embryos further established that, quantitatively, the iron concentration found in the nucleus was higher than in the expected iron-rich organelles such as plastids or vacuoles. Moreover, within the nucleus, iron was particularly accumulated in a subcompartment that was identified as the nucleolus as it was shown to transiently disassemble during cell division. Taken together, our data uncover an as yet unidentified although abundant iron pool in the cell, which is located in the nuclei of healthy, actively dividing plant tissues. This result paves the way for the discovery of a novel cellular function for iron related to nucleus/nucleolus-associated processes.

  11. Identifying and retargeting transcriptional hot spots in the human genome.

    Science.gov (United States)

    Cheng, Joseph K; Lewis, Amanda M; Kim, Do Soon; Dyess, Timothy; Alper, Hal S

    2016-08-01

    Mammalian cell line development requires streamlined methodologies that will reduce both the cost and time to identify candidate cell lines. Improvements in site-specific genomic editing techniques can result in flexible, predictable, and robust cell line engineering. However, an outstanding question in the field is the specific site of integration. Here, we seek to identify productive loci within the human genome that will result in stable, high expression of heterologous DNA. Using an unbiased, random integration approach and a green fluorescent reporter construct, we identify ten single-integrant, recombinant human cell lines that exhibit stable, high-level expression. From these cell lines, eight unique corresponding integration loci were identified. These loci are concentrated in non-protein coding regions or intronic regions of protein coding genes. Expression mapping of the surrounding genes reveals minimal disruption of endogenous gene expression. Finally, we demonstrate that targeted de novo integration at one of the identified loci, the 12(th) exon-intron region of the GRIK1 gene on chromosome 21, results in superior expression and stability compared to the standard, illegitimate integration approach at levels approaching 4-fold. The information identified here along with recent advances in site-specific genomic editing techniques can lead to expedited cell line development.

  12. Satellite magnetic modeling of north African hot spots

    Science.gov (United States)

    Phillips, R. J.; Brown, C. R.

    1985-01-01

    The primary objectives of the MAGSAT mission was to measure the intensity and direction of magnetization of the Earth's crust. A significant effort was directed to the large crustal anomalies first delineated by the POGO mission. The MAGSAT data are capable of spatial resolution of the crustal field to 250 km wavelength with reliability limits to less than 1 nT in the mean. The difficulties of dealing with less than the most robust of the MAGSAT anomalies is that often there is no more than the magnetic fields themselves to constrain geophysical models of the interior, and no independent means of assessing the quality of the crustal anomaly data in interpreting the subsurface are available.

  13. Copepod carcasses as microbial hot spots for pelagic denitrification

    DEFF Research Database (Denmark)

    Glud, Ronnie N.; Grossart, Hans-Peter; Larsen, Morten;

    2015-01-01

    Copepods are exposed to a high non-predatory mortality and their decomposing carcasses act as microniches with intensified microbial activity. Sinking carcasses could thereby represent anoxic microenvironment sustaining anaerobic microbial pathways in otherwise oxic water columns. Using non-invas...

  14. Denitrification 'hot spots' in soil following surface residue application

    Science.gov (United States)

    Kuntz, Marianne; Morley, Nicholas J.; Hallett, Paul D.; Watson, Christine; Baggs, Elizabeth M.

    2015-04-01

    The availability of organic C is an important driver for the production and reduction of the greenhouse gas nitrous oxide (N2O) during denitrification. Denitrification as a response to plant residue amendments to soil surfaces has been extensively researched. However, the nature of hotspot sites of N2O production and reduction within the soil profile, especially in relation to the location of applied residues, is unknown. In a laboratory experiment we investigated the relationship between denitrifier N2O surface fluxes and N2O production and reduction sites. Probes which equilibrate with the soil gas phase by diffusion were developed to quantify denitrification products and product ratios at 1-2 cm, 4.5-5.5 cm or 8-9 cm from the surface. 13C labelled barley straw was incorporated at rates of 0, 2 and 4 t ha-1 into the top 3 cm of soil and subsequently amended with 14NH415NO3. In a three week experiment the soil gas phase at the three depths was analysed for 15N-N2O, 15N-N2, 13C-CO2 and O2 concentrations. Additionally, cores were destructively sampled for mineral 15N as well as microbial C and dissolved C in the respective depths. 15N-N2O and CO2 surface fluxes peaked one day after N application, with residue application resulting in significantly higher 15N-N2O emission rates compared to the non-amended control. The timing of the 15N-N2O surface flux on day 1 was related to maximum 15N-N2O concentrations of 36.6 μg 15N L-1 within the pore space at 5 cm depth. Three days after fertilizer application 15N-N2O pore space concentrations had significantly increased to 193 μg 15N L-1 at 9 cm depth indicating denitrifier activity at greater depth. Denitrification below the soil surface could be explained by increased microbial activity, oxygen depletion with increasing depth and progressive downwards diffusion of fertilizer NO3-. However, C availability appeared to only affect denitrification in the surface layer in which the residue was incorporated. Our results provide insight into the nature and drivers of 'hotspots' of denitrifier activity within the soil profile. Such information can contribute to the development of sustainable management practices that lower net emissions of N2O from arable soils.

  15. Current-Induced Forces and Hot Spots in Biased Nanojunctions

    DEFF Research Database (Denmark)

    Lu, Jing Tao; Christensen, Rasmus Bjerregaard; Wang, Jian-Sheng;

    2015-01-01

    We investigate theoretically the interplay of current-induced forces (CIFs), Joule heating, and heat transport inside a current-carrying nanoconductor. We find that the CIFs, due to the electron-phonon coherence, can control the spatial heat dissipation in the conductor. This yields a significant...

  16. Coral Mucus Is a Hot Spot for Viral Infections.

    Science.gov (United States)

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-09-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  17. Poisson Spot with Magnetic Levitation

    Science.gov (United States)

    Hoover, Matthew; Everhart, Michael; D'Arruda, Jose

    2010-01-01

    In this paper we describe a unique method for obtaining the famous Poisson spot without adding obstacles to the light path, which could interfere with the effect. A Poisson spot is the interference effect from parallel rays of light diffracting around a solid spherical object, creating a bright spot in the center of the shadow.

  18. Designing Allosteric Control into Enzymes by Chemical Rescue of Structure

    Energy Technology Data Exchange (ETDEWEB)

    Deckert, Katelyn; Budiardjo, S. Jimmy; Brunner, Luke C.; Lovell, Scott; Karanicolas, John (Kansas)

    2012-08-07

    Ligand-dependent activity has been engineered into enzymes for purposes ranging from controlling cell morphology to reprogramming cellular signaling pathways. Where these successes have typically fused a naturally allosteric domain to the enzyme of interest, here we instead demonstrate an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruption and restoration of structure, rather than active site chemistry, as a means to achieve modulate function. We present two examples, W33G in a {beta}-glycosidase enzyme ({beta}-gly) and W492G in a {beta}-glucuronidase enzyme ({beta}-gluc), in which we engineer indole-dependent activity into enzymes by removing a buried tryptophan side chain that serves as a buttress for the active site architecture. In both cases, we observe a loss of function, and in both cases we find that the subsequent addition of indole can be used to restore activity. Through a detailed analysis of {beta}-gly W33G kinetics, we demonstrate that this rescued enzyme is fully functionally equivalent to the corresponding wild-type enzyme. We then present the apo and indole-bound crystal structures of {beta}-gly W33G, which together establish the structural basis for enzyme inactivation and rescue. Finally, we use this designed switch to modulate {beta}-glycosidase activity in living cells using indole. Disruption and recovery of protein structure may represent a general technique for introducing allosteric control into enzymes, and thus may serve as a starting point for building a variety of bioswitches and sensors.

  19. Allosteric activation mechanism of the cys-loop receptors

    Institute of Scientific and Technical Information of China (English)

    Yong-chang CHANG; Wen WU; Jian-liang ZHANG; Yao HUANG

    2009-01-01

    Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of amino-terminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.

  20. Spotting a fake

    International Nuclear Information System (INIS)

    Diamonds are highly prized for their dazzling appearance and hardness, but would you be able to spot one that had been created in the laboratory? Simon Lawson describes how physics-based techniques can distinguish between natural and synthetic stones. For the last 50 years or so we have been able to make synthetic diamonds that replicate the superlative physical and chemical properties of natural diamonds, and these are used largely for industrial applications. But in the mind of the consumer, there is far more to a diamond than its hardness or brilliance. Research commissioned by the Diamond Trading Company (DTC) has shown that 94% of women surveyed prefer natural diamonds over synthetic ones as a symbol of love, possibly as a result of the immense age of natural stones. One of the key research activities at the DTC is therefore to ensure that synthetic diamonds can be spotted easily. (U.K.)

  1. Bioinformatic scaling of allosteric interactions in biomedical isozymes

    Science.gov (United States)

    Phillips, J. C.

    2016-09-01

    Allosteric (long-range) interactions can be surprisingly strong in proteins of biomedical interest. Here we use bioinformatic scaling to connect prior results on nonsteroidal anti-inflammatory drugs to promising new drugs that inhibit cancer cell metabolism. Many parallel features are apparent, which explain how even one amino acid mutation, remote from active sites, can alter medical results. The enzyme twins involved are cyclooxygenase (aspirin) and isocitrate dehydrogenase (IDH). The IDH results are accurate to 1% and are overdetermined by adjusting a single bioinformatic scaling parameter. It appears that the final stage in optimizing protein functionality may involve leveling of the hydrophobic limits of the arms of conformational hydrophilic hinges.

  2. Flying spot scanner

    International Nuclear Information System (INIS)

    An improved flying spot x-ray scanning equipment is described which includes a grid controlled x-ray tube and associated collimators for producing a pencil beam of x-rays. It is possible to control the position of the scan field relative to the patient, to control the width of the scan field and also to independently achieve an arbitary variation in the longitudinal dimension of the scan field. (U.K.)

  3. Allosteric modulators of the hERG K{sup +} channel

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhiyi, E-mail: z.yu@lacdr.leidenuniv.nl; Klaasse, Elisabeth, E-mail: elisabethklaasse@hotmail.com; Heitman, Laura H., E-mail: l.h.heitman@lacdr.leidenuniv.nl; IJzerman, Adriaan P., E-mail: ijzerman@lacdr.leidenuniv.nl

    2014-01-01

    Drugs that block the cardiac K{sup +} channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K{sup +} channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [{sup 3}H]astemizole and [{sup 3}H]dofetilide to the hERG K{sup +} channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC{sub 50} values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC{sub 50} values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K{sup +} channel, which is discussed in the light of findings on other ion channels. - Highlights: • Allosteric modulators on the hERG K{sup +} channel were evaluated in binding assays. • LUF6200 was identified as a potent allosteric inhibitor. • Potassium ions were found to behave as allosteric enhancers. • Positive cooperativity and distinct allosteric sites for them were proposed.

  4. Spot- Zombie Filtering System

    Directory of Open Access Journals (Sweden)

    Arathy Rajagopal

    2014-01-01

    Full Text Available A major security challenge on the Internet is the existence of the large number of compromised machines. Such machines have been increasingly used to launch various security attacks including spamming and spreading malware, DDoS, and identity theft. These compromised machines are called “Zombies”. In general E-mail applications and providers uses spam filters to filter the spam messages. Spam filtering is a technique for discriminating the genuine message from the spam messages. The attackers send the spam messages to the targeted machine by exalting the filters, which causes the increase in false positives and false negatives. We develop an effective spam zombie detection system named SPOT by monitoring outgoing messages of a network. SPOT focuses on the number of outgoing messages that are originated or forwarded by each computer on a network to identify the presence of Zombies. SPOT is designed based on a powerful statistical tool called Sequential Probability Ratio Test, which has bounded false positive and false negative error rates.

  5. Spot- Zombie Filtering System

    Directory of Open Access Journals (Sweden)

    Arathy Rajagopal

    2015-10-01

    Full Text Available A major security challenge on the Internet is the existence of the large number of compromised machines. Such machines have been increasingly used to launch various security attacks including spamming and spreading malware, DDoS, and identity theft. These compromised machines are called "Zombies". In general E-mail applications and providers uses spam filters to filter the spam messages. Spam filtering is a technique for discriminating the genuine message from the spam messages. The attackers send the spam messages to the targeted machine by exalting the filters, which causes the increase in false positives and false negatives. We develop an effective spam zombie detection system named SPOT by monitoring outgoing messages of a network. SPOT focuses on the number of outgoing messages that are originated or forwarded by each computer on a network to identify the presence of Zombies. SPOT is designed based on a powerful statistical tool called Sequential Probability Ratio Test, which has bounded false positive and false negative error rates.

  6. The allosteric switching mechanism in bacteriophage MS2

    Science.gov (United States)

    Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F.

    2016-07-01

    We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.

  7. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  8. Hot Money,Hot Problems

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    After emerging from the economic doldrums, developing economies are now confronted with a new danger-a flood of international hot money. But how has the speculative capital circumvented regulatory controls and what are the consequences concerning the stability of the developing world? Zhao Zhongwei, a senior researcher with the Institute of World Politics and Economics at the Chinese Academy of Social Sciences, discussed these issues in an article recently published in the China Securities Journal. Edited excerpts follow

  9. Cold Spots in Neonatal Incubators Are Hot Spots for Microbial Contamination

    NARCIS (Netherlands)

    de Goffau, Marcus C.; Bergman, Klasien A.; de Vries, Hendrik J.; Meessen, Nico E. L.; Degener, John E.; van Dijl, Jan Maarten; Harmsen, Hermie J. M.

    2011-01-01

    Thermal stability is essential for the survival and well-being of preterm neonates. This is achieved in neonatal incubators by raising the ambient temperature and humidity to sufficiently high levels. However, potentially pathogenic microorganisms also can thrive in such warm and humid environments.

  10. Hot Spots and Not Spots: Addressing Infrastructure and Service Provision through Combined Approaches in Rural Scotland

    OpenAIRE

    Sarah Skerratt

    2010-01-01

    There is widespread acceptance that the absence or presence of infrastructure and services in rural areas can lead to cycles of decline or resilience in these localities. It is also accepted that in remoter areas, population sparsity leads to a higher unit cost for delivery of services and infrastructure, and that private sector providers do not find such areas attractive for investment. At the same time, there is a reduction in spending capability within the public sector due to the signific...

  11. Analysis on hot spot mutations of GJB2 gene and mitochondrial DNA 12S rRNA among consanguineous induced deafness families%近亲婚配致聋家系中患者GJB2和线粒体DNA 12S rRNA基因突变热点分析

    Institute of Scientific and Technical Information of China (English)

    杨威; 付四清; 董家曙; 王春芳; 陈观明

    2011-01-01

    Objective: To analyze the frequencies of hot spot mutations of the two common deafness gene - GJB2 and mitochondrial DNA 12S rRNA in the consanguineous induced deafness families. Methods: 25 consanguineous induced deafness families received comprehensive physical examination and pure tone test, 48 cases were found, 3 mi venous blood samples were obtained to extract DNA, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) targeted to specific genes were performed, the cases with mutation were confirmed by gene sequencing. Results: 1 case was found with 235delC homozygous mutation of GJB2 gene, 3 cases were found with heterozygous mutation; no A 1555G mutation was found in mitochondrial DNA 12S rRNA. Conclusion: The most of consanguineous induced deafness are autosomal recessive inheritance, but the incidence of 235delC mutation of GJB2 gene is low.%目的:分析GJB2和线粒体DNA 12S rRNA两种常见耳聋致病基因突变热点在近亲婚配致聋家系患者中的发生频率.方法:对25个近亲结婚致聋核心家系的后代进行全面的体格检查和纯音测试,共发现患者48例,采静脉血3 ml,提取DNA,针对特定基因,进行聚合酶链式反应(Polymerase chain reaction,PCR)及限制性片段长度多态性(Restriction fragmentlength polymorphism,RFLP)分析,发现突变者测序验证.结果:发现GJB2基因235delC纯合突变1例,杂合突变3例;未发现线粒体DNA 12S rRNA A1555G突变.结论:近亲结婚家系中遗传性聋多为常染色体隐性遗传,但GJB2基因235delc突变的发生率较低.

  12. The Spotting Distribution of Wildfires

    Directory of Open Access Journals (Sweden)

    Jonathan Martin

    2016-06-01

    Full Text Available In wildfire science, spotting refers to non-local creation of new fires, due to downwind ignition of brands launched from a primary fire. Spotting is often mentioned as being one of the most difficult problems for wildfire management, because of its unpredictable nature. Since spotting is a stochastic process, it makes sense to talk about a probability distribution for spotting, which we call the spotting distribution. Given a location ahead of the fire front, we would like to know how likely is it to observe a spot fire at that location in the next few minutes. The aim of this paper is to introduce a detailed procedure to find the spotting distribution. Most prior modelling has focused on the maximum spotting distance, or on physical subprocesses. We will use mathematical modelling, which is based on detailed physical processes, to derive a spotting distribution. We discuss the use and measurement of this spotting distribution in fire spread, fire management and fire breaching. The appendix of this paper contains a comprehensive review of the relevant underlying physical sub-processes of fire plumes, launching fire brands, wind transport, falling and terminal velocity, combustion during transport, and ignition upon landing.

  13. 我国高等医学教育慕课研究热点的共词聚类分析%Hot spots analysis for MOOC research of higher medical education in our country based on co-word clustering

    Institute of Scientific and Technical Information of China (English)

    李深情; 陈思达; 钱丽欢; 李静; 梁沛华; 方春平; 刘步平

    2016-01-01

    Objective To analyze the hot research spots of MOOC research of higher medical edu-cation in China. Methods We searched the database of China National Knowledge Infrastrucure (CNKI), VIP database of Chinese journal (VIP), Wanfang Database for published studies on MOOC research of higher medical education from 2005 to April 2015. The high frequency words were counted by an analysis program-Bibliographic Item Co-occurrence Matrix Builder (BICOMB). According to the ranking word frequency threshold formula by Donohue, we collected the high-frequency keywords. The corresponding co-word ma-trixes were constructed by Bibexcel, then the data was input into SPSS 19.0 software for hierarchical clus-tering analysis. Results Finally 2 459 articles were included. 11 177 keywords and 13 high frequency words (the number of the real selected was 24) were taken into account. The keywords “stanford” clus-tered with “education module”, “online education”, “online courses”, “distance education”, “learning pro-cess”, “self-regulated learning”, “information technology”, “classroom teaching”. The keywords “network course” clustered with “teaching design”. The keywords “online learning” clustered with itself. The key-words “challenge” clustered with “colleges and universities”. The keywords “flipped classroom” clustered with“micro-lecture”,“MOOC”,“higher education”, “library”, “teaching module”, “teaching reform”, “big data”,“open education”. The keywords“SPOC”clustered with itself. Conclusion The research of MOOC research of higher medical education in our country has formed the basic characteristics with six hot spots involving teaching design, the model of online learning, dispassion thinking, teaching reform, and develop-ment. And there are many potential areas.%目的:分析我国高等医学教育慕课研究的热点。方法检索中国学术期刊全文数据库(CNKI)、维普

  14. Coarse-Grained Molecular Simulations of Allosteric Cooperativity

    CERN Document Server

    Nandigrami, Prithviraj

    2015-01-01

    Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate binding affinities and control binding sensitivity to ligand concentration. In this paper, we investigate the structural origins of binding affinity and allosteric cooperativity of binding two calcium ions to each domain of calmodulin (CaM) through simulations of a simple coarse-grained model. In this model, the protein's conformational transitions between open and closed conformational ensembles are simulated explicitly and ligand binding and unbinding is treated implicitly at the mean field level. Ligand binding is cooperative because the binding sites are coupled through a shift in the dominant conformational ensemble upon binding. The classic Monod-Wyman-Changeux model of allostery with appropriate binding free energy to the open and closed ensembles accurately describe...

  15. Architecture and Co-Evolution of Allosteric Materials

    CERN Document Server

    Yan, Le; Brito, Carolina; Wyart, Matthieu

    2016-01-01

    We introduce a numerical scheme to evolve functional materials that can accomplish a specified mechanical task. In this scheme, the number of solutions, their spatial architectures and the correlations among them can be computed. As an example, we consider an "allosteric" task, which requires the material to respond specifically to a stimulus at a distant active site. We find that functioning materials evolve a less-constrained trumpet-shaped region connecting the stimulus and active sites and that the amplitude of the elastic response varies non-monotonically along the trumpet. As previously shown for some proteins, we find that correlations appearing during evolution alone are sufficient to identify key aspects of this design. Finally, we show that the success of this architecture stems from the emergence of soft edge modes recently found to appear near the surface of marginally connected materials. Overall, our in silico evolution experiment offers a new window to study the relationship between structure, ...

  16. Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei; Chun, Eugene; Thompson, Aaron A.; Chubukov, Pavel; Xu, Fei; Katritch, Vsevolod; Han, Gye Won; Roth, Christopher B.; Heitman, Laura H.; IJzerman, Adriaan P.; Cherezov, Vadim; Stevens, Raymond C. (Scripps); (Leiden/Amsterdam); (Receptos)

    2012-08-31

    Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A{sub 2A} adenosine receptor by replacing its third intracellular loop with apocytochrome b{sub 562}RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp{sup 2.50}. Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function.

  17. The SPOT satellite

    Science.gov (United States)

    Fouquet, J.-P.

    1981-03-01

    The background, objectives and data products of the French SPOT remote sensing satellite system are presented. The system, which was developed starting in 1978 with the subsequent participation of Sweden and Belgium, is based on a standard multimission platform with associated ground control station and a mission-specific payload, which includes two High-Resolution Visible range instruments allowing the acquisition of stereoscopic views from different orbits. Mission objectives include the definition of future remote sensing systems, the compilation of a cartographic and resources data base, the study of species discrimination and production forecasting based on frequent access and off-nadir viewing, the compilation of a stereoscopic data base, and platform and instrument qualification, for possible applications in cartography, geology and agriculture. Standard data products will be available at three levels of preprocessing: radiometric correction only, precision processing for vertical viewing, and cartographic quality processing.

  18. Allosteric control in a metalloprotein dramatically alters function.

    Science.gov (United States)

    Baxter, Elizabeth Leigh; Zuris, John A; Wang, Charles; Vo, Phu Luong T; Axelrod, Herbert L; Cohen, Aina E; Paddock, Mark L; Nechushtai, Rachel; Onuchic, Jose N; Jennings, Patricia A

    2013-01-15

    Metalloproteins (MPs) comprise one-third of all known protein structures. This diverse set of proteins contain a plethora of unique inorganic moieties capable of performing chemistry that would otherwise be impossible using only the amino acids found in nature. Most of the well-studied MPs are generally viewed as being very rigid in structure, and it is widely thought that the properties of the metal centers are primarily determined by the small fraction of amino acids that make up the local environment. Here we examine both theoretically and experimentally whether distal regions can influence the metal center in the diabetes drug target mitoNEET. We demonstrate that a loop (L2) 20 Å away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster and orders of magnitude effects on the rate of [2Fe-2S] cluster transfer to an apo-acceptor protein. These surprising effects occur in the absence of any structural changes. An examination of the native basin dynamics of the protein using all-atom simulations shows that twisting in L2 controls scissoring in the cluster binding domain and results in perturbations to one of the cluster-coordinating histidines. These allosteric effects are in agreement with previous folding simulations that predicted L2 could communicate with residues surrounding the metal center. Our findings suggest that long-range dynamical changes in the protein backbone can have a significant effect on the functional properties of MPs.

  19. Positive allosteric feedback regulation of the stringent response enzyme RelA by its product

    OpenAIRE

    Shyp, Viktoriya; Tankov, Stoyan; Ermakov, Andrey; Kudrin, Pavel; English, Brian P.; Ehrenberg, Måns; Tenson, Tanel; Elf, Johan; Hauryliuk, Vasili

    2012-01-01

    This report identifies a new mechanism of enzyme activation—positive allosteric regulation by the product—in the context of the bacterial stringent response, which is essential for bacterial adaptation to environmental conditions.

  20. Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors – A Structural Perspective of Ligands and Mutants

    Science.gov (United States)

    Harpsøe, Kasper; Isberg, Vignir; Tehan, Benjamin G.; Weiss, Dahlia; Arsova, Angela; Marshall, Fiona H.; Bräuner-Osborne, Hans; Gloriam, David E.

    2015-01-01

    The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far this has not led to a marketed drug, largely because of the difficulties in achieving subtype-selective compounds with desired properties. Very recently the first crystal structures were published for the transmembrane domain of two metabotropic glutamate receptors in complex with negative allosteric modulators. In this analysis, we make the first comprehensive structural comparison of all metabotropic glutamate receptors, placing selective negative allosteric modulators and critical mutants into the detailed context of the receptor binding sites. A better understanding of how the different mGlu allosteric modulator binding modes relates to selective pharmacological actions will be very valuable for rational design of safer drugs. PMID:26359761

  1. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1

    DEFF Research Database (Denmark)

    Hindie, Valerie; Stroba, Adriana; Zhang, Hua;

    2009-01-01

    Protein phosphorylation transduces a large set of intracellular signals. One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. Previous work described an allosteric site mediating phosphorylation-d...

  2. Allosteric Optical Control of a Class B G-Protein-Coupled Receptor.

    Science.gov (United States)

    Broichhagen, Johannes; Johnston, Natalie R; von Ohlen, Yorrick; Meyer-Berg, Helena; Jones, Ben J; Bloom, Stephen R; Rutter, Guy A; Trauner, Dirk; Hodson, David J

    2016-05-01

    Allosteric regulation promises to open up new therapeutic avenues by increasing drug specificity at G-protein-coupled receptors (GPCRs). However, drug discovery efforts are at present hampered by an inability to precisely control the allosteric site. Herein, we describe the design, synthesis, and testing of PhotoETP, a light-activated positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR involved in the maintenance of glucose homeostasis in humans. PhotoETP potentiates Ca(2+) , cAMP, and insulin responses to glucagon-like peptide-1 and its metabolites following illumination of cells with blue light. PhotoETP thus provides a blueprint for the production of small-molecule class B GPCR allosteric photoswitches, and may represent a useful tool for understanding positive cooperativity at the GLP-1R. PMID:27059784

  3. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C;

    2011-01-01

    molecules often act more deeply in an allosteric mode. However, opposed to the well described molecular interaction of allosteric modulators in class C 7-transmembrane helix (7TM) receptors, the interaction in class A, to which the chemokine receptors belong, is more sparsely described. Using the CCR5...... chemokine receptor as a model system, we studied the molecular interaction and conformational interchange required for proper action of various orthosteric chemokines and allosteric small molecules, including the well known CCR5 antagonists TAK-779, SCH-C, and aplaviroc, and four novel CCR5 ago......-allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...

  4. Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model*

    OpenAIRE

    Morgan, Hugh P.; McNae, Iain W.; Matthew W Nowicki; Hannaert, Véronique; Michels, Paul A M; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.

    2010-01-01

    Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognizable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase, from Leishmania mexicana. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6° rigi...

  5. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    OpenAIRE

    Stephen Verespy III; Mehta, Akul Y.; Daniel Afosah; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated...

  6. Structure-Based Statistical Mechanical Model Accounts for the Causality and Energetics of Allosteric Communication.

    Science.gov (United States)

    Guarnera, Enrico; Berezovsky, Igor N

    2016-03-01

    Allostery is one of the pervasive mechanisms through which proteins in living systems carry out enzymatic activity, cell signaling, and metabolism control. Effective modeling of the protein function regulation requires a synthesis of the thermodynamic and structural views of allostery. We present here a structure-based statistical mechanical model of allostery, allowing one to observe causality of communication between regulatory and functional sites, and to estimate per residue free energy changes. Based on the consideration of ligand free and ligand bound systems in the context of a harmonic model, corresponding sets of characteristic normal modes are obtained and used as inputs for an allosteric potential. This potential quantifies the mean work exerted on a residue due to the local motion of its neighbors. Subsequently, in a statistical mechanical framework the entropic contribution to allosteric free energy of a residue is directly calculated from the comparison of conformational ensembles in the ligand free and ligand bound systems. As a result, this method provides a systematic approach for analyzing the energetics of allosteric communication based on a single structure. The feasibility of the approach was tested on a variety of allosteric proteins, heterogeneous in terms of size, topology and degree of oligomerization. The allosteric free energy calculations show the diversity of ways and complexity of scenarios existing in the phenomenology of allosteric causality and communication. The presented model is a step forward in developing the computational techniques aimed at detecting allosteric sites and obtaining the discriminative power between agonistic and antagonistic effectors, which are among the major goals in allosteric drug design. PMID:26939022

  7. Dissection of the conduit for allosteric control of carbamoyl phosphate synthetase by ornithine.

    Science.gov (United States)

    Pierrat, Olivier A; Javid-Majd, Farah; Raushel, Frank M

    2002-04-01

    Ornithine is an allosteric activator of carbamoyl phosphate synthetase (CPS) from Escherichia coli. Nine amino acids in the vicinity of the binding sites for ornithine and potassium were mutated to alanine, glutamine, or lysine. The residues E783, T1042, and T1043 were found to be primarily responsible for the binding of ornithine to CPS, while E783 and E892, located within the carbamate domain of the large subunit, were necessary for the transmission of the allosteric signals to the active site. In the K loop for the binding of the monovalent cation potassium, only E761 was crucial for the exhibition of the allosteric effects of ornithine, UMP, and IMP. The mutations H781K and S792K altered significantly the allosteric properties of ornithine, UMP, and IMP, possibly by modifying the conformation of the K-loop structure. Overall, these mutations affected the allosteric properties of ornithine and IMP more than those of UMP. The mutants S792K and D1041A altered the allosteric regulation by ornithine and IMP in a similar way, suggesting common features in the activation mechanism exhibited by these two effectors. PMID:11913967

  8. Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P+-dependent malic enzyme.

    Directory of Open Access Journals (Sweden)

    Ju-Yi Hsieh

    Full Text Available Human mitochondrial NAD(P+-dependent malic enzyme (m-NAD(P-ME is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P-ME_R67A/R91A and m-NAD(P-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P-ME enzyme activity.

  9. Detection and analysis of the hot spots of ATP7B gene mutation in the members of a family with an adult Wilson's disease%成人Wilson病一家系成员P型铜转运三磷酸腺苷酶基因突变热区的检测和分析

    Institute of Scientific and Technical Information of China (English)

    朱永豹; 黄元成; 郭威; 陈韬

    2012-01-01

    Objective To make a early gene diagnosis and analyze the mutation characteristics of ATP7B gene by detecting the hot spots of ATP7B gene mutation in Chinese family patients with Wilson's disease. Methods The genomic DNA of the family members were extracted from peripheral blood. The fragments of exon 8,1243 of ATP7B gene were amplified by polymerase chain reaction and PCR products were sequenced bidirectionally. Then we analyzed the results with BLAST software online. Results I 1N I 2( proband) , II1 and II2 have heterozygote missense mutation Arg778Leu(2333G > T) and heterozy-gote nonsense mutation Leu770Leu (2310C>G) on exon 8. I 1 、 I 2, I 3 and II1 have heterozygote mis-sense mutation Lys952Arg(2855A >G) on exon 12. All the subjects have no mutations on exon 13. Conclusion Exon 8、12,13 of ATP7B gene should be detected in the members of a family with a proband having Wilson' s disease, which will help to diagnose pre-symptomatic patients and carriers earlier.%目的 通过检测中国人Wilson病(WD)P型铜转运三磷酸腺苷酶(ATP7B)基因突变热区,对成人WD一家系成员进行早期基因诊断和突变特征分析.方法 提取该家系成员外周血基因组DNA,采用聚合酶链反应扩增ATP7B基因第8、12、13号外显子,并对扩增产物进行直接双向测序,然后应用在线BLAST软件分析.结果 Ⅰ1、Ⅰ2(先证者)、Ⅱ1和Ⅱ2第8号外显子存在Arg778Leu(2333G> T)错义杂合突变,且均伴有Leu770Leu( 2310C>G)同义杂合突变;Ⅰ1、Ⅰ 2、Ⅰ3和Ⅱ1第12号外显子存在Lys952Arg(2855A>G)错义杂合突变;所有受检者第13号外显子均未存在突变.结论 对有先证者的Wilson病家系成员应进行ATP7B基因第8、12、13号外显子检测,有助于早期发现症状前患者和携带者.

  10. 经导管消融选择性去肾交感神经治疗——未来心力衰竭治疗的热点%Catheter-based Selective Renal Artery Sympathetic Denervation-A Hot Spot of Managing Heart Failure in the Future

    Institute of Scientific and Technical Information of China (English)

    刘晓莉; 肖培林

    2013-01-01

    心力衰竭是各种心脏疾病的终末阶段.近几十年来,心力衰竭的治疗得到了一定的发展,但仍不能明显改善患者生存率,且需长期大量服药,严重影响患者生活质量.大量的研究显示:交感神经系统激活在心力衰竭的发生发展中扮演着重要角色.自上世纪40、50年代,学者们已开始进行去交感神经治疗心力衰竭的尝试,但碍于当时设备和技术的限制,治疗效果不尽人意.可喜的是,澳大利亚的权威学者近几年在美国心脏病学会/美国心脏协会心血管年会上介绍了一种安全、有效的新型去肾交感神经的方法,即经导管消融选择性去肾交感神经.该研究证实此方法可以明显降低全身交感活性.那么经导管消融去肾交感神经治疗能否成为未来心力衰竭治疗的热点呢?现将对去交感神经治疗心力衰竭的现状和进展做一综述.%Heart failure is the end-stage of serious heart disease. In recent decades, the heart failure treatment has gained some devel -opment, but still can' t significantly improve survival rate. The patients need to take a large amount of medication , and influence seriously the life quality of patients. Some study demonstrated that the somatic sympathetic nerves drive plays an important role in the development of heart failure. The sympathetic nerves denervation therapy has been researched since 1940 ~ 1950s, but the result is not satisfactory because of the restriction of poor technology. On the 2009 ACC/AHA cardiovascular annual conference , Krum MD introduced a new therapeutic method: the catheter-based renal artery ablation renal sympathetic nerves denervation . The HTN-2 Trail prove that the new method is safe and effective. The study (HTN-2) has been confirmed that the method can obviously reduce the whole body sympathetic activity . Will the catheter-based selective renal artery sympathetic denervation be a hot spot of managing heart failure in the future

  11. Perspective of International Research Hot Spot in the Field of Workplace Learning--Based on the Study of Literature from Seven Western Academic Journals Between 2005 and 2015%工作场所学习领域国际研究热点透视*--基于西方7本学术期刊文献(2005~2015)

    Institute of Scientific and Technical Information of China (English)

    张艳超; 黄健

    2016-01-01

    Workplace learning has become a new research territory of educational science in recent years. It has caused the wide attention from scholars both at home and abroad. With the help of Scopus database, based on the study of literature from seven academic journals between 2005 and 2015 in the West, the method of literature metrology, clustering analysis, mapping knowledge domain and so on have been used to do the data analysis and some results have been found. Firstly, the SCImago Journal Rank of these academic journals is generally low and the academic influence needs to be strengthened in the field of workplace learning. Secondly, the scholars have a clear gap between home and abroad concerning the research level and the achievements in this field. Actually, the United States, the Commonwealth and the Nordic countries have become the academic centers of international workplace learning research. Thirdly,"Human Resource Development"and"Workplace Learning"have become the two major mainstream research camps in the field of workplace learning, and the trend of their convergence and fusion is being strengthened. Fourthly, the characteristics of interdisciplinary research are obvious in the field of workplace learning. Interdisciplinary research from education, management, organization, psychology, sociology, etc. is benefit for academic innovation. Through the perspective of the international hot spot and development trend in the field of workplace learning, it can be expected that the studies of informal learning, gender, organizational learning, action learning and leadership development have important academic value and space to be explored in the future. It deserves the attention of scholars.%近年来工作场所学习领域已然成为教育科学研究的新疆域,引起了国内外学者的广泛关注。借助Scopus数据库,以西方工作场所学习领域7本学术期刊2005~2015年度收录的文献为研究样本,采用文献计量、聚类分析、

  12. Volatile Abundances and the Deep Cloud Structure in Jupiter's Great Red Spot

    Science.gov (United States)

    Bjoraker, Gordon; de Pater, Imke; Wong, Michael H.; Adamkovics, Mate; Hewagama, Tilak; Hesman, Brigette

    2016-10-01

    Despite the presence of thick upper level clouds, Jupiter's Great Red Spot preserves the signature of physical conditions at much deeper levels in the troposphere. The Great Red Spot is dark at 5 microns due to thick clouds, but imaging alone does not reveal which cloud layers are responsible for attenuating this radiation. We used NIRSPEC on the Keck telescope and CSHELL on the Infrared Telescope Facility to spectrally resolve line profiles of CH3D and other molecules on Jupiter in order to derive the pressure of the line formation region in the 5-micron window. Variations in CH3D line shape with position on Jupiter are due to cloud structure rather than changes in gas mole fraction.By aligning the slit east/west on Jupiter, we sampled the Great Red Spot and a Hot Spot at the same latitude. The profile of the CH3D lines is very broad in the Hot Spot due to collisions with up to 8 bars of H2, where unit optical depth due to collision induced H2 opacity occurs. The extreme width of these CH3D features implies that Hot Spots do not have significant cloud opacity where water is expected to condense. Within the Great Red Spot, the line profiles are substantially narrower than in the Hot Spot. The best fit to the line shape of CH3D requires an opaque cloud at 5 bars, which we identify as being a water cloud. Thermal radiation from the 5-bar level is further attenuated by upper level clouds, but these colder clouds do not change the shape of the spectrum. Once we have established a cloud structure, gas mole fractions may then be retrieved. Gaseous H2O is clearly evident in the Great Red Spot, which provides independent evidence that we are sounding deep in Jupiter's atmosphere. A combination of Keck and IRTF data allows us to retrieve NH3, PH3, and gaseous H2O inside the Hot Spot and within the Great Red Spot. This technique can be applied to study the deep cloud structure anywhere on Jupiter whether or not upper level clouds are present. We will use this technique to

  13. Hydrologic indicators of hot spots and hot moments of mercury methylation potential along river corridors.

    Science.gov (United States)

    Singer, Michael Bliss; Harrison, Lee R; Donovan, Patrick M; Blum, Joel D; Marvin-DiPasquale, Mark

    2016-10-15

    The biogeochemical cycling of metals and other contaminants in river-floodplain corridors is controlled by microbial activity responding to dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, inundation history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this within a Northern California river system with a legacy of landscape-scale 19th century hydraulic gold mining. We combine hydraulic modeling, Hg measurements in sediment and biota, and first-order calculations of mercury transformation to assess the potential role of river floodplains in producing monomethylmercury (MMHg), a neurotoxin which accumulates in local and migratory food webs. We identify frequently inundated floodplain areas, as well as floodplain areas inundated for long periods. We quantify the probability of MMHg production potential (MPP) associated with hydrology in each sector of the river system as a function of the spatial patterns of overbank inundation and drainage, which affect long-term redox history of contaminated sediments. Our findings identify river floodplains as periodic, temporary, yet potentially important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the hydrologic record. We suggest that inundation is an important driver of MPP in river corridors and that the entire flow history must be analyzed retrospectively in terms of inundation magnitude and frequency in order to accurately assess biogeochemical risks, rather than merely highlighting the largest floods or low-flow periods. MMHg bioaccumulation within the aquatic food web in this system may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn. There is a long-term pattern of MPP under the current flow regime that is likely to be accentuated by increasingly common large floods with extended duration. PMID:26994752

  14. Hydrologic indicators of hot spots and hot moments of mercury methylation potential along river corridors

    Science.gov (United States)

    Singer, Michael B.; Harrison, Lee R.; Donovan, Patrick M.; Blum, Joel D.; Marvin-DiPasquale, Mark C.

    2016-01-01

    The biogeochemical cycling of metals and other contaminants in river-floodplain corridors is controlled by microbial activity responding to dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, inundation history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this within a Northern California river system with a legacy of landscape-scale 19th century hydraulic gold mining. We combine hydraulic modeling, Hg measurements in sediment and biota, and first-order calculations of mercury transformation to assess the potential role of river floodplains in producing monomethylmercury (MMHg), a neurotoxin which accumulates in local and migratory food webs. We identify frequently inundated floodplain areas, as well as floodplain areas inundated for long periods. We quantify the probability of MMHg production potential (MPP) associated with hydrology in each sector of the river system as a function of the spatial patterns of overbank inundation and drainage, which affect long-term redox history of contaminated sediments. Our findings identify river floodplains as periodic, temporary, yet potentially important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the hydrologic record. We suggest that inundation is an important driver of MPP in river corridors and that the entire flow history must be analyzed retrospectively in terms of inundation magnitude and frequency in order to accurately assess biogeochemical risks, rather than merely highlighting the largest floods or low-flow periods. MMHg bioaccumulation within the aquatic food web in this system may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn. There is a long-term pattern of MPP under the current flow regime that is likely to be accentuated by increasingly common large floods with extended duration.

  15. Hot Spots and Hot Moments in Scientific Collaborations and Social Movements

    Science.gov (United States)

    Parker, John N.; Hackett, Edward J.

    2012-01-01

    Emotions are essential but little understood components of research; they catalyze and sustain creative scientific work and fuel the scientific and intellectual social movements (SIMs) that propel scientific change. Adopting a micro-sociological focus, we examine how emotions shape two intellectual processes central to all scientific work:…

  16. Hot particles in industrial waste and mining tailings

    CERN Document Server

    Selchau-Hansen, K; Freyer, K; Treutler, C; Enge, W

    1999-01-01

    Industrial waste was studied concerning its radioactive pollution. Using known properties of the solid state nuclear track detector CR-39 we found among a high concentration of more or less homogeneously distributed single alpha-tracks discrete spots of very high enrichments of alpha-particles created by so called hot particles. We will report about the alpha-activity, the concentration of hot particles and about their ability to be air borne.

  17. Are AMPA receptor positive allosteric modulators potential pharmacotherapeutics for addiction?

    Science.gov (United States)

    Watterson, Lucas R; Olive, M Foster

    2013-01-01

    Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications. PMID:24380895

  18. Computational Investigation on the Allosteric Modulation of Androgen Receptor

    Institute of Scientific and Technical Information of China (English)

    OU Min-Rui; LI Jun-Qian

    2012-01-01

    Androgens have similar structures with different biological activities. To identify molecular determinants responsible for the activity difference, we have docked six steroidal androgens to the binding site or the surface of androgen receptor by using molecular docking with computational investigation. The energy was calculated respectively based on the QM (quantum mechanics) and MM (molecular mechanics) methods. The result shows that the allosteric modulation of androgen receptor plays an important role in the binding process between androgens and receptor. The open state receptor is less stable than the close state one, but the latter is more favorable for binding with androgens. It is worthy of note that when the androgen receptors binding or without binding with androgen are in close state, they are difficult to return to their open state. This phenomenon is an exception of the well known two-state model theory in which the two states are reversible. Whether the internal of close state androgen receptor has a combination of androgen or not, the androgen receptor surface can be combined with another androgen, and their surface binding energies could be very close. The result is consistent with the experimental observations, but this phenomenon of continuous combination from open state is also an exception of the two-state model theory.

  19. Allosteric receptor activation by the plant peptide hormone phytosulfokine.

    Science.gov (United States)

    Wang, Jizong; Li, Hongju; Han, Zhifu; Zhang, Heqiao; Wang, Tong; Lin, Guangzhong; Chang, Junbiao; Yang, Weicai; Chai, Jijie

    2015-09-10

    Phytosulfokine (PSK) is a disulfated pentapeptide that has a ubiquitous role in plant growth and development. PSK is perceived by its receptor PSKR, a leucine-rich repeat receptor kinase (LRR-RK). The mechanisms underlying the recognition of PSK, the activation of PSKR and the identity of the components downstream of the initial binding remain elusive. Here we report the crystal structures of the extracellular LRR domain of PSKR in free, PSK- and co-receptor-bound forms. The structures reveal that PSK interacts mainly with a β-strand from the island domain of PSKR, forming an anti-β-sheet. The two sulfate moieties of PSK interact directly with PSKR, sensitizing PSKR recognition of PSK. Supported by biochemical, structural and genetic evidence, PSK binding enhances PSKR heterodimerization with the somatic embryogenesis receptor-like kinases (SERKs). However, PSK is not directly involved in PSKR-SERK interaction but stabilizes PSKR island domain for recruitment of a SERK. Our data reveal the structural basis for PSKR recognition of PSK and allosteric activation of PSKR by PSK, opening up new avenues for the design of PSKR-specific small molecules. PMID:26308901

  20. Adenine nucleotides as allosteric effectors of PEA seed glutamine synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Unkefer, P.J.; Knight, T.J.

    1986-05-01

    The energy charge in the plant cell has been proposed as a regulator of glutamine synthetase (GS) activity. The authors have shown that 2.1 moles of ..gamma..(/sup 32/P)-ATP were bound/mole subunits of purified pea seed GS during complete inactivation with methionine sulfoximine. Since GS has one active site per subunit, the second binding site provides the potential for allosteric regulation of GS by adenine nucleotides. The authors have investigated the inhibition of the ATP-dependent synthetic activity by ADP and AMP. ADP and AMP cannot completely inhibit GS; but ATP does overcome the inhibition by ADP and AMP as shown by plots of % inhibition vs inhibitor concentration. This indicates that inhibition of GS by ADP or AMP is not completely due to competitive inhibition. In the absence of ADP or AMP, double reciprocal plots for ATP are linear below 10 mM; however, in the presence of either ADP or AMP these pots are curvilinear downwards. The ratio of Vm/asymptote is less than 1. The Hill number for ATP in the absence of ADP or AMP is 0.93 but decreases with increasing ADP or AMP to a value of 0.28 with 10 mM ADP. These data are consistent with negative cooperativity by ADP and AMP. Thus, as the ADP/ATP or AMP/ATP ratios are increased GS activity decreases. This is consistent with regulation of GS activity by energy charge in planta.

  1. Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain.

    Science.gov (United States)

    Burgess, Selena G; Oleksy, Arkadiusz; Cavazza, Tommaso; Richards, Mark W; Vernos, Isabelle; Matthews, David; Bayliss, Richard

    2016-07-01

    The vast majority of clinically approved protein kinase inhibitors target the ATP-binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects. Allosteric inhibitors are generally more selective, but are difficult to identify because allosteric binding sites are often unknown or poorly characterized. Aurora-A is activated through binding of TPX2 to an allosteric site on the kinase catalytic domain, and this knowledge could be exploited to generate an inhibitor. Here, we generated an allosteric inhibitor of Aurora-A kinase based on a synthetic, vNAR single domain scaffold, vNAR-D01. Biochemical studies and a crystal structure of the Aurora-A/vNAR-D01 complex show that the vNAR domain overlaps with the TPX2 binding site. In contrast with the binding of TPX2, which stabilizes an active conformation of the kinase, binding of the vNAR domain stabilizes an inactive conformation, in which the αC-helix is distorted, the canonical Lys-Glu salt bridge is broken and the regulatory (R-) spine is disrupted by an additional hydrophobic side chain from the activation loop. These studies illustrate how single domain antibodies can be used to characterize the regulatory mechanisms of kinases and provide a rational basis for structure-guided design of allosteric Aurora-A kinase inhibitors. PMID:27411893

  2. Allosteric inhibition of the NS2B-NS3 protease from dengue virus.

    Science.gov (United States)

    Yildiz, Muslum; Ghosh, Sumana; Bell, Jeffrey A; Sherman, Woody; Hardy, Jeanne A

    2013-12-20

    Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition. This method identified a new allosteric site utilizing a circumscribed panel of just eight cysteine variants and only five cysteine reactive probes. The allosterically sensitive site is centered at Ala125, between the 120s loop and the 150s loop. The crystal structures of WT and modified NS2B-NS3pro demonstrate that the 120s loop is flexible. Our work suggests that binding at this site prevents a conformational rearrangement of the NS2B region of the protein, which is required for activation. Preventing this movement locks the protein into the open, inactive conformation, suggesting that this site may be useful in the future development of therapeutic allosteric inhibitors. PMID:24164286

  3. Characteristic features of kynurenine aminotransferase allosterically regulated by (alpha-ketoglutarate in cooperation with kynurenine.

    Directory of Open Access Journals (Sweden)

    Ken Okada

    Full Text Available Kynurenine aminotransferase from Pyrococcus horikoshii OT3 (PhKAT, which is a homodimeric protein, catalyzes the conversion of kynurenine (KYN to kynurenic acid (KYNA. We analyzed the transaminase reaction mechanisms of this protein with pyridoxal-5'-phosphate (PLP, KYN and α-ketoglutaric acid (2OG or oxaloacetic acid (OXA. 2OG significantly inhibited KAT activities in kinetic analyses, suggesting that a KYNA biosynthesis is allosterically regulated by 2OG. Its inhibitions evidently were unlocked by KYN. 2OG and KYN functioned as an inhibitor and activator in response to changes in the concentrations of KYN and 2OG, respectively. The affinities of one subunit for PLP or 2OG were different from that of the other subunit, as confirmed by spectrophotometry and isothermal titration calorimetry, suggesting that the difference of affinities between subunits might play a role in regulations of the KAT reaction. Moreover, we identified two active and allosteric sites in the crystal structure of PhKAT-2OG complexes. The crystal structure of PhKAT in complex with four 2OGs demonstrates that two 2OGs in allosteric sites are effector molecules which inhibit the KYNA productions. Thus, the combined data lead to the conclusion that PhKAT probably is regulated by allosteric control machineries, with 2OG as the allosteric inhibitor.

  4. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

    Science.gov (United States)

    Dror, Ron O.; Green, Hillary F.; Valant, Celine; Borhani, David W.; Valcourt, James R.; Pan, Albert C.; Arlow, Daniel H.; Canals, Meritxell; Lane, J. Robert; Rahmani, Raphaël; Baell, Jonathan B.; Sexton, Patrick M.; Christopoulos, Arthur; Shaw, David E.

    2013-11-01

    The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15Å from the classical, `orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

  5. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

    Science.gov (United States)

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A.; Bernardi, Anna; Colombo, Giorgio

    2016-04-01

    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone’s active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.

  6. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    Science.gov (United States)

    Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  7. The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

    DEFF Research Database (Denmark)

    Hudson, Brian D; Ulven, Trond; Milligan, Graeme

    2013-01-01

    G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand. As therapeutics, allosteric ligands possess many theoretical advantages over their orthosteric counterparts, including more complex modes of action, improved...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

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

    Science.gov (United States)

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

    2016-10-01

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

  9. NMR Characterization of Information Flow and Allosteric Communities in the MAP Kinase p38γ.

    Science.gov (United States)

    Aoto, Phillip C; Martin, Bryan T; Wright, Peter E

    2016-01-01

    The intramolecular network structure of a protein provides valuable insights into allosteric sites and communication pathways. However, a straightforward method to comprehensively map and characterize these pathways is not currently available. Here we present an approach to characterize intramolecular network structure using NMR chemical shift perturbations. We apply the method to the mitogen activated protein kinase (MAPK) p38γ. p38γ contains allosteric sites that are conserved among eukaryotic kinases as well as unique to the MAPK family. How these regulatory sites communicate with catalytic residues is not well understood. Using our method, we observe and characterize for the first time information flux between regulatory sites through a conserved kinase infrastructure. This network is accessed, reinforced, and broken in various states of p38γ, reflecting the functional state of the protein. We demonstrate that the approach detects critical junctions in the network corresponding to biologically significant allosteric sites and pathways. PMID:27353957

  10. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

    Science.gov (United States)

    Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

    2015-11-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.

  11. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

    Science.gov (United States)

    Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

    2015-01-01

    Inosine-5′-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches. PMID:26558346

  12. A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.

    Science.gov (United States)

    Foda, Zachariah H; Shan, Yibing; Kim, Eric T; Shaw, David E; Seeliger, Markus A

    2015-01-01

    Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity. PMID:25600932

  13. Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel.

    Science.gov (United States)

    Yu, Zhiyi; van Veldhoven, Jacobus P D; 't Hart, Ingrid M E; Kopf, Adrian H; Heitman, Laura H; IJzerman, Adriaan P

    2015-12-01

    We synthesized and evaluated a series of compounds for their allosteric modulation at the Kv11.1 (hERG) channel. Most compounds were negative allosteric modulators of [(3)H]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known Kv11.1 blockers. PMID:26519929

  14. Implication of spot position error on plan quality and patient safety in pencil-beam-scanning proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Juan; Beltran, Chris J., E-mail: beltran.chris@mayo.edu; Herman, Michael G. [Division of Medical Physics, Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2014-08-15

    Purpose: To quantitatively and systematically assess dosimetric effects induced by spot positioning error as a function of spot spacing (SS) on intensity-modulated proton therapy (IMPT) plan quality and to facilitate evaluation of safety tolerance limits on spot position. Methods: Spot position errors (PE) ranging from 1 to 2 mm were simulated. Simple plans were created on a water phantom, and IMPT plans were calculated on two pediatric patients with a brain tumor of 28 and 3 cc, respectively, using a commercial planning system. For the phantom, a uniform dose was delivered to targets located at different depths from 10 to 20 cm with various field sizes from 2{sup 2} to 15{sup 2} cm{sup 2}. Two nominal spot sizes, 4.0 and 6.6 mm of 1 σ in water at isocenter, were used for treatment planning. The SS ranged from 0.5 σ to 1.5 σ, which is 2–6 mm for the small spot size and 3.3–9.9 mm for the large spot size. Various perturbation scenarios of a single spot error and systematic and random multiple spot errors were studied. To quantify the dosimetric effects, percent dose error (PDE) depth profiles and the value of percent dose error at the maximum dose difference (PDE [ΔDmax]) were used for evaluation. Results: A pair of hot and cold spots was created per spot shift. PDE[ΔDmax] is found to be a complex function of PE, SS, spot size, depth, and global spot distribution that can be well defined in simple models. For volumetric targets, the PDE [ΔDmax] is not noticeably affected by the change of field size or target volume within the studied ranges. In general, reducing SS decreased the dose error. For the facility studied, given a single spot error with a PE of 1.2 mm and for both spot sizes, a SS of 1σ resulted in a 2% maximum dose error; a SS larger than 1.25 σ substantially increased the dose error and its sensitivity to PE. A similar trend was observed in multiple spot errors (both systematic and random errors). Systematic PE can lead to noticeable hot

  15. The therapeutic promise of positive allosteric modulation of nicotinic receptors.

    Science.gov (United States)

    Uteshev, Victor V

    2014-03-15

    In the central nervous system, deficits in cholinergic neurotransmission correlate with decreased attention and cognitive impairment, while stimulation of neuronal nicotinic acetylcholine receptors improves attention, cognitive performance and neuronal resistance to injury as well as produces robust analgesic and anti-inflammatory effects. The rational basis for the therapeutic use of orthosteric agonists and positive allosteric modulators (PAMs) of nicotinic receptors arises from the finding that functional nicotinic receptors are ubiquitously expressed in neuronal and non-neuronal tissues including brain regions highly vulnerable to traumatic and ischemic types of injury (e.g., cortex and hippocampus). Moreover, functional nicotinic receptors do not vanish in age-, disease- and trauma-related neuropathologies, but their expression and/or activation levels decline in a subunit- and brain region-specific manner. Therefore, augmenting the endogenous cholinergic tone by nicotinic agents is possible and may offset neurological impairments associated with cholinergic hypofunction. Importantly, because neuronal damage elevates extracellular levels of choline (a selective agonist of α7 nicotinic acetylcholine receptors) near the site of injury, α7-PAM-based treatments may augment pathology-activated α7-dependent auto-therapies where and when they are most needed (i.e., in the penumbra, post-injury). Thus, nicotinic-PAM-based treatments are expected to augment the endogenous cholinergic tone in a spatially and temporally restricted manner creating the potential for differential efficacy and improved safety as compared to exogenous orthosteric nicotinic agonists that activate nicotinic receptors indiscriminately. In this review, I will summarize the existing trends in therapeutic applications of nicotinic PAMs.

  16. Hemoglobin and the origins of the concept of allosterism.

    Science.gov (United States)

    Edsall, J T

    1980-02-01

    heterotropic interactions. Brief final comments relate to the evolution of the concept of reversible conformational transitions as the basis for both homotropic and heterotropic interactions in allosteric proteins. PMID:6986293

  17. Organism-adapted specificity of the allosteric regulation of pyruvate kinase in lactic acid bacteria.

    Directory of Open Access Journals (Sweden)

    Nadine Veith

    Full Text Available Pyruvate kinase (PYK is a critical allosterically regulated enzyme that links glycolysis, the primary energy metabolism, to cellular metabolism. Lactic acid bacteria rely almost exclusively on glycolysis for their energy production under anaerobic conditions, which reinforces the key role of PYK in their metabolism. These organisms are closely related, but have adapted to a huge variety of native environments. They include food-fermenting organisms, important symbionts in the human gut, and antibiotic-resistant pathogens. In contrast to the rather conserved inhibition of PYK by inorganic phosphate, the activation of PYK shows high variability in the type of activating compound between different lactic acid bacteria. System-wide comparative studies of the metabolism of lactic acid bacteria are required to understand the reasons for the diversity of these closely related microorganisms. These require knowledge of the identities of the enzyme modifiers. Here, we predict potential allosteric activators of PYKs from three lactic acid bacteria which are adapted to different native environments. We used protein structure-based molecular modeling and enzyme kinetic modeling to predict and validate potential activators of PYK. Specifically, we compared the electrostatic potential and the binding of phosphate moieties at the allosteric binding sites, and predicted potential allosteric activators by docking. We then made a kinetic model of Lactococcus lactis PYK to relate the activator predictions to the intracellular sugar-phosphate conditions in lactic acid bacteria. This strategy enabled us to predict fructose 1,6-bisphosphate as the sole activator of the Enterococcus faecalis PYK, and to predict that the PYKs from Streptococcus pyogenes and Lactobacillus plantarum show weaker specificity for their allosteric activators, while still having fructose 1,6-bisphosphate play the main activator role in vivo. These differences in the specificity of allosteric

  18. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

    DEFF Research Database (Denmark)

    Hassing, Helle A; Fares, Suzan; Larsen, Olav;

    2016-01-01

    for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR......231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far....

  19. Laser based spot weld characterization

    Science.gov (United States)

    Jonietz, Florian; Myrach, Philipp; Rethmeier, Michael; Suwala, Hubert; Ziegler, Mathias

    2016-02-01

    Spot welding is one of the most important joining technologies, especially in the automotive industry. Hitherto, the quality of spot welded joints is tested mainly by random destructive tests. A nondestructive testing technique offers the benefit of cost reduction of the testing procedure and optimization of the fabrication process, because every joint could be examined. This would lead to a reduced number of spot welded joints, as redundancies could be avoided. In the procedure described here, the spot welded joint between two zinc-coated steel sheets (HX340LAD+Z100MB or HC340LA+ZE 50/50) is heated optically on one side. Laser radiation and flash light are used as heat sources. The melted zone, the so called "weld nugget" provides the mechanical stability of the connection, but also constitutes a thermal bridge between the sheets. Due to the better thermal contact, the spot welded joint reveals a thermal behavior different from the surrounding material, where the heat transfer between the two sheets is much lower. The difference in the transient thermal behavior is measured with time resolved thermography. Hence, the size of the thermal contact between the two sheets is determined, which is directly correlated to the size of the weld nugget, indicating the quality of the spot weld. The method performs well in transmission with laser radiation and flash light. With laser radiation, it works even in reflection geometry, thus offering the possibility of testing with just one-sided accessibility. By using heating with collimated laser radiation, not only contact-free, but also remote testing is feasible. A further convenience compared to similar thermographic approaches is the applicability on bare steel sheets without any optical coating for emissivity correction. For this purpose, a proper way of emissivity correction was established.

  20. Friction Stir Spot Welding of Advanced High Strength Steels

    Energy Technology Data Exchange (ETDEWEB)

    Hovanski, Yuri; Santella, M. L.; Grant, Glenn J.

    2009-12-28

    Friction stir spot welding was used to join two advanced high-strength steels using polycrystalline cubic boron nitride tooling. Numerous tool designs were employed to study the influence of tool geometry on weld joints produced in both DP780 and a hot-stamp boron steel. Tool designs included conventional, concave shouldered pin tools with several pin configurations; a number of shoulderless designs; and a convex, scrolled shoulder tool. Weld quality was assessed based on lap shear strength, microstructure, microhardness, and bonded area. Mechanical properties were functionally related to bonded area and joint microstructure, demonstrating the necessity to characterize processing windows based on tool geometry.

  1. Color tunable LED spot lighting

    Science.gov (United States)

    Hoelen, C.; Ansems, J.; Deurenberg, P.; van Duijneveldt, W.; Peeters, M.; Steenbruggen, G.; Treurniet, T.; Valster, A.; ter Weeme, J. W.

    2006-08-01

    A new trend in illumination is to use dynamic light to set or dynamically vary the ambience of a room or office. For this we need color tunable spots that can reliably vary over at least a wide range of color temperatures, and preferably also more saturated colors. LEDs are in principle ideally suited for this application thanks to their nature of emitting light in a relatively narrow band. For color tunable spot lighting based on the concept of mixing RGB LED colors, the key results have been presented before. Limitations of these 3-intrinsic-color mixing systems with high color rendering properties are found in a limited operating temperature range due to wavelength shifts, a limited color temperature range, and a low maximum operating temperature due to a strong flux decrease with increasing temperature. To overcome these limitations, a 3-color R pcGB system with phosphor-converted red (R pc) and a 4-color RAGB system have been investigated. With both systems, a CRI of at least 80 can be maintained over the relevant color temperature range of approximately 2700 K to 6500 K. In this paper we compare these concepts on overall system aspects and report on the performance of prototype spot lamps. The main features of the RAGB and R pcGB spot lamp concepts can be summarized as: 1) The RAGB spot overcomes CRI and gamut shortcomings of RGB light sources and gives much freedom in wavelength selection, but suffers from temperature sensitivity and complex controls; 2) The R pcGB spot overcomes shortcomings concerning CRI and thermal dependence of RGB sources and enables relatively simple controls, but needs an improved overall red efficacy. With both color concepts, prototype spot lamps have been built. The amber to red emitting nitridosilicate-based phosphors can be wavelength-tuned for optimal performance, which is found at a peak emission around 610 nm for high color quality systems. This results in a simple and very robust system with good color consistency. For the

  2. Is this Red Spot the Blue Spot (locus ceruleum)?

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Won Sick; Lee, Yu Kyung; Lee, Min Kyung; Hwang, Kyung Hoon [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2010-06-15

    The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleum. The locus ceruleum is called the blue spot and known to be a center of the norepinephrinergic system.

  3. Fatal Spotted Fever Rickettsiosis, Kenya

    OpenAIRE

    Rutherford, Jeremiah S.; Macaluso, Kevin; Smith, Nathaniel; Zaki, Sherif R.; Paddock, Christopher D.; Davis, Jon; Peterso, Norman; Azad, Abdu F.; Rosenberg, Ronald

    2004-01-01

    We report a fatal case of rickettsiosis in a woman from the United States living in Kenya, who had a history of tick exposure. Immunohistochemical staining of skin, kidney, and liver demonstrated spotted fever group rickettsiae. The clinical findings, severity, and fatal outcome are most consistent with Rickettsia conorii infection.

  4. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    Science.gov (United States)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-08-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

  5. Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase.

    Science.gov (United States)

    Zhang, Shengnan; Fitzpatrick, Paul F

    2016-04-01

    Liver phenylalanine hydroxylase (PheH) is an allosteric enzyme that requires activation by phenylalanine for full activity. The location of the allosteric site for phenylalanine has not been established. NMR spectroscopy of the isolated regulatory domain (RDPheH(25-117) is the regulatory domain of PheH lacking residues 1-24) of the rat enzyme in the presence of phenylalanine is consistent with formation of a side-by-side ACT dimer. Six residues in RDPheH(25-117) were identified as being in the phenylalanine-binding site on the basis of intermolecular NOEs between unlabeled phenylalanine and isotopically labeled protein. The location of these residues is consistent with two allosteric sites per dimer, with each site containing residues from both monomers. Site-specific variants of five of the residues (E44Q, A47G, L48V, L62V, and H64N) decreased the affinity of RDPheH(25-117) for phenylalanine based on the ability to stabilize the dimer. Incorporation of the A47G, L48V, and H64N mutations into the intact protein increased the concentration of phenylalanine required for activation. The results identify the location of the allosteric site as the interface of the regulatory domain dimer formed in activated PheH.

  6. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway.

    Science.gov (United States)

    Alverez, Celeste; Bulfer, Stacie L; Chakrasali, Ramappa; Chimenti, Michael S; Deshaies, Raymond J; Green, Neal; Kelly, Mark; LaPorte, Matthew G; Lewis, Taber S; Liang, Mary; Moore, William J; Neitz, R Jeffrey; Peshkov, Vsevolod A; Walters, Michael A; Zhang, Feng; Arkin, Michelle R; Wipf, Peter; Huryn, Donna M

    2016-02-11

    A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts. PMID:26985295

  7. Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.

    Science.gov (United States)

    Mony, Laetitia; Zhu, Shujia; Carvalho, Stéphanie; Paoletti, Pierre

    2011-06-17

    NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.

  8. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes.

    Science.gov (United States)

    Nowosinski, Karol; von Krbek, Larissa K S; Traulsen, Nora L; Schalley, Christoph A

    2015-10-16

    A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

  9. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    Science.gov (United States)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-01-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

  10. Computational predictions suggest that structural similarity in viral polymerases may lead to comparable allosteric binding sites.

    Science.gov (United States)

    Brown, Jodian A; Espiritu, Marie V; Abraham, Joel; Thorpe, Ian F

    2016-08-15

    The identification of ligand-binding sites is often the first step in drug targeting and design. To date there are numerous computational tools available to predict ligand binding sites. These tools can guide or mitigate the need for experimental methods to identify binding sites, which often require significant resources and time. Here, we evaluate four ligand-binding site predictor (LBSP) tools for their ability to predict allosteric sites within the Hepatitis C Virus (HCV) polymerase. Our results show that the LISE LBSP is able to identify all three target allosteric sites within the HCV polymerase as well as a known allosteric site in the Coxsackievirus polymerase. LISE was then employed to identify novel binding sites within the polymerases of the Dengue, West Nile, and Foot-and-mouth Disease viruses. Our results suggest that all three viral polymerases have putative sites that share structural or chemical similarities with allosteric pockets of the HCV polymerase. Thus, these binding locations may represent an evolutionarily conserved structural feature of several viral polymerases that could be exploited for the development of small molecule therapeutics. PMID:27262620

  11. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65.

    Science.gov (United States)

    Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K; Zhu, Hu; Chen, Xin; Moy, Sheryl S; Saddoris, Kara A; Nikolova, Viktoriya D; Farrell, Martilias S; Wang, Sheng; Mangano, Thomas J; Deshpande, Deepak A; Jiang, Alice; Penn, Raymond B; Jin, Jian; Koller, Beverly H; Kenakin, Terry; Shoichet, Brian K; Roth, Bryan L

    2015-11-26

    At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

  12. Elastic network model of allosteric regulation in protein kinase PDK1

    Directory of Open Access Journals (Sweden)

    Williams Gareth

    2010-05-01

    Full Text Available Abstract Background Structural switches upon binding of phosphorylated moieties underpin many signalling networks. The ligand activation is a form of allosteric modulation of the protein, where the binding site is remote from the structural change in the protein. Recently this structural switch has been elegantly demonstrated with the crystallisation of the activated form of 3-phosphoinositide-dependent protein kinase-1 (PDK1. The purpose of the present work is to determine whether the allosteric coupling in PDK1 emerges at the level of a simple coarse grained model of protein dynamics. Results It is shown here that the allosteric effects of the agonist binding to the small lobe upon the activation loop in the large lobe of PDK1 are explainable within a simple 'ball and spring' elastic network model (ENM of protein dynamics. In particular, the model shows that the bound phospho peptide mimetic fluctuations have a high degree of correlation with the activation loop of PDK1. Conclusions The ENM approach to small molecule activation of proteins may offer a first pass predictive methodology where affinity is encoded in residues remote from the active site, and aid in the design of specific protein agonists that enhance the allosteric coupling and antagonist that repress it.

  13. Allosteric Regulation of the Rotational Speed in a Light-Driven Molecular Motor

    NARCIS (Netherlands)

    Faulkner, Adele; van Leeuwen, Thomas; Feringa, Ben L; Wezenberg, Sander J

    2016-01-01

    The rotational speed of an overcrowded alkene-based molecular rotary motor, having an integrated 4,5-diazafluorenyl coordination motif, can be regulated allosterically via the binding of metal ions. DFT calculations have been used to predict the relative speed of rotation of three different (i.e. zi

  14. Coherent conformational degrees of freedom as a structural basis for allosteric communication.

    Directory of Open Access Journals (Sweden)

    Simon Mitternacht

    2011-12-01

    Full Text Available Conformational changes in allosteric regulation can to a large extent be described as motion along one or a few coherent degrees of freedom. The states involved are inherent to the protein, in the sense that they are visited by the protein also in the absence of effector ligands. Previously, we developed the measure binding leverage to find sites where ligand binding can shift the conformational equilibrium of a protein. Binding leverage is calculated for a set of motion vectors representing independent conformational degrees of freedom. In this paper, to analyze allosteric communication between binding sites, we introduce the concept of leverage coupling, based on the assumption that only pairs of sites that couple to the same conformational degrees of freedom can be allosterically connected. We demonstrate how leverage coupling can be used to analyze allosteric communication in a range of enzymes (regulated by both ligand binding and post-translational modifications and huge molecular machines such as chaperones. Leverage coupling can be calculated for any protein structure to analyze both biological and latent catalytic and regulatory sites.

  15. An Allosteric Receptor by Simultaneous "Casting" and "Molding" in a Dynamic Combinatorial Library

    NARCIS (Netherlands)

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2015-01-01

    Allosteric synthetic receptors are difficult to access by design. Herein we report a dynamic combinatorial strategy towards such systems based on the simultaneous use of two different templates. Through a process of simultaneous casting (the assembly of a library member around a template) and moldin

  16. Steric hindrance mutagenesis in the conserved extracellular vestibule impedes allosteric binding of antidepressants to the serotonin transporter

    DEFF Research Database (Denmark)

    Plenge, Per; Shi, Lei; Beuming, Thijs;

    2012-01-01

    be involved in the allosteric binding in the extracellular vestibule located above the central substrate binding (S1) site. Indeed, mutagenesis of selected residues in the vestibule reduces the allosteric potency of (S)-citalopram and clomipramine. The identified site is further supported by the inhibitory...... effects of Zn(2+) binding in an engineered site and the covalent attachment of benzocaine-methanethiosulfonate to a cysteine introduced in the extracellular vestibule. The data provide a mechanistic explanation for the allosteric action of antidepressants at SERT and suggest that the role of the vestibule...

  17. Rational design of allosteric-inhibition sites in classical protein tyrosine phosphatases

    Science.gov (United States)

    Chio, Cynthia M.; Yu, Xiaoling; Bishop, Anthony C.

    2015-01-01

    Protein tyrosine phosphatases (PTPs), which catalyze the dephosphorylation of phosphotyrosine in protein substrates, are critical regulators of metazoan cell signaling and have emerged as potential drug targets for a range of human diseases. Strategies for chemically targeting the function of individual PTPs selectively could serve to elucidate the signaling roles of these enzymes and would potentially expedite validation of the therapeutic promise of PTP inhibitors. Here we report a novel strategy for the design of non-natural allosteric-inhibition sites in PTPs; these sites, which can be introduced into target PTPs through protein engineering, serve to sensitize target PTPs to potent and selective inhibition by a biarsenical small molecule. Building on the recent discovery of a naturally occurring cryptic allosteric site in wild-type Src-homology-2 domain containing PTP (Shp2) that can be targeted by biarsenical compounds, we hypothesized that Shp2’s unusual sensitivity to biarsenicals could be strengthened through rational design and that the Shp2-specific site could serve as a blueprint for the introduction of non-natural inhibitor sensitivity in other PTPs. Indeed, we show here that the strategic introduction of a cysteine residue at a position removed from the Shp2 active site can serve to increase the potency and selectivity of the interaction between Shp2’s allosteric site and the biarsenical inhibitor. Moreover, we find that “Shp2-like” allosteric sites can be installed de novo in PTP enzymes that do not possess naturally occurring sensitivity to biarsenical compounds. Using primary-sequence alignments to guide our enzyme engineering, we have successfully introduced allosteric-inhibition sites in four classical PTPs—PTP1B, PTPH-1, FAP-1, and HePTP—from four different PTP subfamilies, suggesting that our sensitization approach can likely be applied widely across the classical PTP family to generate biarsenical-responsive PTPs. PMID:25828055

  18. Scalable rule-based modelling of allosteric proteins and biochemical networks.

    Directory of Open Access Journals (Sweden)

    Julien F Ollivier

    Full Text Available Much of the complexity of biochemical networks comes from the information-processing abilities of allosteric proteins, be they receptors, ion-channels, signalling molecules or transcription factors. An allosteric protein can be uniquely regulated by each combination of input molecules that it binds. This "regulatory complexity" causes a combinatorial increase in the number of parameters required to fit experimental data as the number of protein interactions increases. It therefore challenges the creation, updating, and re-use of biochemical models. Here, we propose a rule-based modelling framework that exploits the intrinsic modularity of protein structure to address regulatory complexity. Rather than treating proteins as "black boxes", we model their hierarchical structure and, as conformational changes, internal dynamics. By modelling the regulation of allosteric proteins through these conformational changes, we often decrease the number of parameters required to fit data, and so reduce over-fitting and improve the predictive power of a model. Our method is thermodynamically grounded, imposes detailed balance, and also includes molecular cross-talk and the background activity of enzymes. We use our Allosteric Network Compiler to examine how allostery can facilitate macromolecular assembly and how competitive ligands can change the observed cooperativity of an allosteric protein. We also develop a parsimonious model of G protein-coupled receptors that explains functional selectivity and can predict the rank order of potency of agonists acting through a receptor. Our methodology should provide a basis for scalable, modular and executable modelling of biochemical networks in systems and synthetic biology.

  19. Rocky Mountain Spotted Fever: Statistics and Epidemiology

    Science.gov (United States)

    ... The CDC Cancel Submit Search The CDC Rocky Mountain Spotted Fever (RMSF) Note: Javascript is disabled or ... please visit this page: About CDC.gov . Rocky Mountain Spotted Fever (RMSF) Symptoms, Diagnosis, and Treatment Statistics ...

  20. Improvements on analytic modelling of stellar spots

    CERN Document Server

    Montalto, M; Oshagh, M; Boisse, I; Bruno, G; Santos, N C

    2014-01-01

    In this work we present the solution of the stellar spot problem using the Kelvin-Stokes theorem. Our result is applicable for any given location and dimension of the spots on the stellar surface. We present explicitely the result up to the second degree in the limb darkening law. This technique can be used to calculate very efficiently mutual photometric effects produced by eclipsing bodies occulting stellar spots and to construct complex spot shapes.

  1. 9 CFR 149.4 - Spot audit.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Spot audit. 149.4 Section 149.4... LIVESTOCK IMPROVEMENT VOLUNTARY TRICHINAE CERTIFICATION PROGRAM § 149.4 Spot audit. (a) In addition to regularly scheduled site audits, certified production sites will be subject to spot audits. (1) Random...

  2. Heating of Jupiter's upper atmosphere above the Great Red Spot

    Science.gov (United States)

    O'Donoghue, James; Moore, Luke; Stallard, Tom; Melin, Henrik

    2016-10-01

    Measured upper-atmospheric, mid-to-low latitude temperatures of the giant planets are hundreds of degrees warmer than simulations based on solar heating alone can explain. Modelling studies, focused on additional sources of heating, have been so far unable to resolve this significant model-data discrepancy. Equatorward transport of energy from the hot auroral regions was expected to heat low latitude regions; instead, models have demonstrated that auroral energy is trapped at high latitudes, a consequence of the strong Coriolis forces on these rapidly rotating planets. Wave heating, driven from below, represents another potential source of upper-atmospheric heating. Using data taken in 2012 by the ground-based NASA IRTF, we found through observations of the H3+ ion that the upper atmosphere above Jupiter's Great Red Spot (GRS) - the largest storm in the solar system - is hundreds of degrees hotter than anywhere else on the planet. Specifically, the result shows that the northern region of the spot was over 1600 K, and that background temperatures away from the spot are ~850 K. The hotspot, by process of elimination, must be heated from below, and this detection is therefore strong evidence for coupling between Jupiter's lower and upper atmospheres, likely the result of upward propagating acoustic and/or gravity waves. Our results indicate that the lower atmosphere may yet play an important role in resolving the giant planet 'energy crisis'.

  3. Interpreting spotted dolphin age distributions

    OpenAIRE

    Barlow, Jay; Hohn, Aleta A.

    1984-01-01

    Previous work has determined the age distribution from a sample of spotted dolphins (Stenella attenuata) killed in the eastern Pacific tuna purse-seine fishery. In this paper we examine the usefulness of this age distribution for estimating natural mortality rates. The observed age distribution has a deficiency of individuals from 5-15 years and cannot represent a stable age distribution. Sampling bias and errors in age interpretation are examined as possible causes of the "dip" in the obs...

  4. Resistance Spot Welding of dissimilar Steels

    Directory of Open Access Journals (Sweden)

    Ladislav Kolařík

    2012-01-01

    Full Text Available This paper presents an analysis of the properties of resistance spot welds between low carbon steel and austenitic CrNi stainless steel. The thickness of the welded dissimilar materials was 2 mm. A DeltaSpot welding gun with a process tape was used for welding the dissimilar steels. Resistance spot welds were produced with various welding parameters (welding currents ranging from 7 to 8 kA. Light microscopy, microhardness measurements across the welded joints, and EDX analysis were used to evaluate the quality of the resistance spot welds. The results confirm the applicability of DeltaSpot welding for this combination of materials.

  5. Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems.

    Science.gov (United States)

    Ghanakota, Phani; Carlson, Heather A

    2016-08-25

    Mixed-solvent molecular dynamics (MixMD) is a hotspot-mapping technique that relies on molecular dynamics simulations of proteins in binary solvent mixtures. Previous work on MixMD has established the technique's effectiveness in capturing binding sites of small organic compounds. In this work, we show that MixMD can identify both competitive and allosteric sites on proteins. The MixMD approach embraces full protein flexibility and allows competition between solvent probes and water. Sites preferentially mapped by probe molecules are more likely to be binding hotspots. There are two important requirements for the identification of ligand-binding hotspots: (1) hotspots must be mapped at very high signal-to-noise ratio and (2) the hotspots must be mapped by multiple probe types. We have developed our mapping protocol around acetonitrile, isopropanol, and pyrimidine as probe solvents because they allowed us to capture hydrophilic, hydrophobic, hydrogen-bonding, and aromatic interactions. Charged probes were needed for mapping one target, and we introduce them in this work. In order to demonstrate the robust nature and wide applicability of the technique, a combined total of 5 μs of MixMD was applied across several protein targets known to exhibit allosteric modulation. Most notably, all the protein crystal structures used to initiate our simulations had no allosteric ligands bound, so there was no preorganization of the sites to predispose the simulations to find the allosteric hotspots. The protein test cases were ABL Kinase, Androgen Receptor, CHK1 Kinase, Glucokinase, PDK1 Kinase, Farnesyl Pyrophosphate Synthase, and Protein-Tyrosine Phosphatase 1B. The success of the technique is demonstrated by the fact that the top-four sites solely map the competitive and allosteric sites. Lower-ranked sites consistently map other biologically relevant sites, multimerization interfaces, or crystal-packing interfaces. Lastly, we highlight the importance of including protein

  6. Hot Dry Rock; Geothermal Energy

    Energy Technology Data Exchange (ETDEWEB)

    None

    1990-01-01

    The commercial utilization of geothermal energy forms the basis of the largest renewable energy industry in the world. More than 5000 Mw of electrical power are currently in production from approximately 210 plants and 10 000 Mw thermal are used in direct use processes. The majority of these systems are located in the well defined geothermal generally associated with crustal plate boundaries or hot spots. The essential requirements of high subsurface temperature with huge volumes of exploitable fluids, coupled to environmental and market factors, limit the choice of suitable sites significantly. The Hot Dry Rock (HDR) concept at any depth originally offered a dream of unlimited expansion for the geothermal industry by relaxing the location constraints by drilling deep enough to reach adequate temperatures. Now, after 20 years intensive work by international teams and expenditures of more than $250 million, it is vital to review the position of HDR in relation to the established geothermal industry. The HDR resource is merely a body of rock at elevated temperatures with insufficient fluids in place to enable the heat to be extracted without the need for injection wells. All of the major field experiments in HDR have shown that the natural fracture systems form the heat transfer surfaces and that it is these fractures that must be for geothermal systems producing from naturally fractured formations provide a basis for directing the forthcoming but, equally, they require accepting significant location constraints on HDR for the time being. This paper presents a model HDR system designed for commercial operations in the UK and uses production data from hydrothermal systems in Japan and the USA to demonstrate the reservoir performance requirements for viable operations. It is shown that these characteristics are not likely to be achieved in host rocks without stimulation processes. However, the long term goal of artificial geothermal systems developed by systematic

  7. Watermarking spot colors in packaging

    Science.gov (United States)

    Reed, Alastair; Filler, TomáÅ.¡; Falkenstern, Kristyn; Bai, Yang

    2015-03-01

    In January 2014, Digimarc announced Digimarc® Barcode for the packaging industry to improve the check-out efficiency and customer experience for retailers. Digimarc Barcode is a machine readable code that carries the same information as a traditional Universal Product Code (UPC) and is introduced by adding a robust digital watermark to the package design. It is imperceptible to the human eye but can be read by a modern barcode scanner at the Point of Sale (POS) station. Compared to a traditional linear barcode, Digimarc Barcode covers the whole package with minimal impact on the graphic design. This significantly improves the Items per Minute (IPM) metric, which retailers use to track the checkout efficiency since it closely relates to their profitability. Increasing IPM by a few percent could lead to potential savings of millions of dollars for retailers, giving them a strong incentive to add the Digimarc Barcode to their packages. Testing performed by Digimarc showed increases in IPM of at least 33% using the Digimarc Barcode, compared to using a traditional barcode. A method of watermarking print ready image data used in the commercial packaging industry is described. A significant proportion of packages are printed using spot colors, therefore spot colors needs to be supported by an embedder for Digimarc Barcode. Digimarc Barcode supports the PANTONE spot color system, which is commonly used in the packaging industry. The Digimarc Barcode embedder allows a user to insert the UPC code in an image while minimizing perceptibility to the Human Visual System (HVS). The Digimarc Barcode is inserted in the printing ink domain, using an Adobe Photoshop plug-in as the last step before printing. Since Photoshop is an industry standard widely used by pre-press shops in the packaging industry, a Digimarc Barcode can be easily inserted and proofed.

  8. Spotted hyena from north China

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Acomplete fossil skeleton of spotted hyena unearthed on 26 July, 2008 in nearly perfect preservation, exhilarates CAS paleontologists, as the discovery in north China might offer new clues about the interactions between prehistoric faunas of Africa and Eurasia, and meanwhile afford a clue to the big extinction of large amount of species occurring about 11,000 years ago. Hinting at possible connections between species from Africa and Eurasia, the discovery would even provide new insights into the "out-of-Africa" model of human origins.

  9. Allosteric Regulation of Unidirectional Spring-like Motion of Double-Stranded Helicates.

    Science.gov (United States)

    Suzuki, Yoshimasa; Nakamura, Taiki; Iida, Hiroki; Ousaka, Naoki; Yashima, Eiji

    2016-04-13

    We report the unprecedented allosteric regulation of the extension and contraction motions of double-stranded spiroborate helicates composed of 4,4'-linked 2,2'-bipyridine (bpy) and its N,N'-dioxide units in the middle of ortho-linked tetraphenol strands. NMR and circular dichroism measurements and an X-ray crystallographic analysis along with theoretical calculations revealed that enantiomeric helicates contract and extend upon the binding and release of protons and/or metal ions at the covalently linked two binding bpy or N,N'-dioxide moieties without racemization, respectively, regulated by a cooperative anti-syn conformational change of the two bpy or N,N'-dioxide moieties. These anti-syn conformational changes that occurred at the linkages are amplified into a large-scale molecular motion of the helicates leading to reversible spring-like motions coupled with twisting in one direction in a highly homotropic allosteric fashion. PMID:26910831

  10. Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel.

    Science.gov (United States)

    Joseph, Thomas T; Mincer, Joshua S

    2016-01-01

    General anesthetics bind reversibly to ion channels, modifying their global conformational distributions, but the underlying atomic mechanisms are not completely known. We examine this issue by way of the model protein Gloeobacter violaceous ligand-gated ion channel (GLIC) using computational molecular dynamics, with a coarse-grained model to enhance sampling. We find that in flooding simulations, both propofol and a generic particle localize to the crystallographic transmembrane anesthetic binding region, and that propofol also localizes to an extracellular region shared with the crystallographic ketamine binding site. Subsequent simulations to probe these binding modes in greater detail demonstrate that ligand binding induces structural asymmetry in GLIC. Consequently, we employ residue interaction correlation analysis to describe the internal allosteric network underlying the coupling of ligand and distant effector sites necessary for conformational change. Overall, the results suggest that the same allosteric network may underlie the actions of various anesthetics, regardless of binding site. PMID:27403526

  11. Structural Determinants Defining the Allosteric Inhibition of an Essential Antibiotic Target.

    Science.gov (United States)

    Soares da Costa, Tatiana P; Desbois, Sebastien; Dogovski, Con; Gorman, Michael A; Ketaren, Natalia E; Paxman, Jason J; Siddiqui, Tanzeela; Zammit, Leanne M; Abbott, Belinda M; Robins-Browne, Roy M; Parker, Michael W; Jameson, Geoffrey B; Hall, Nathan E; Panjikar, Santosh; Perugini, Matthew A

    2016-08-01

    Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step in the lysine biosynthesis pathway of bacteria. The pathway can be regulated by feedback inhibition of DHDPS through the allosteric binding of the end product, lysine. The current dogma states that DHDPS from Gram-negative bacteria are inhibited by lysine but orthologs from Gram-positive species are not. The 1.65-Å resolution structure of the Gram-negative Legionella pneumophila DHDPS and the 1.88-Å resolution structure of the Gram-positive Streptococcus pneumoniae DHDPS bound to lysine, together with comprehensive functional analyses, show that this dogma is incorrect. We subsequently employed our crystallographic data with bioinformatics, mutagenesis, enzyme kinetics, and microscale thermophoresis to reveal that lysine-mediated inhibition is not defined by Gram staining, but by the presence of a His or Glu at position 56 (Escherichia coli numbering). This study has unveiled the molecular determinants defining lysine-mediated allosteric inhibition of bacterial DHDPS. PMID:27427481

  12. The magic spot: a ppGpp binding site on E. coli RNA polymerase responsible for regulation of transcription initiation.

    Science.gov (United States)

    Ross, Wilma; Vrentas, Catherine E; Sanchez-Vazquez, Patricia; Gaal, Tamas; Gourse, Richard L

    2013-05-01

    The global regulatory nucleotide ppGpp ("magic spot") regulates transcription from a large subset of Escherichia coli promoters, illustrating how small molecules can control gene expression promoter-specifically by interacting with RNA polymerase (RNAP) without binding to DNA. However, ppGpp's target site on RNAP, and therefore its mechanism of action, has remained unclear. We report here a binding site for ppGpp on E. coli RNAP, identified by crosslinking, protease mapping, and analysis of mutant RNAPs that fail to respond to ppGpp. A strain with a mutant ppGpp binding site displays properties characteristic of cells defective for ppGpp synthesis. The binding site is at an interface of two RNAP subunits, ω and β', and its position suggests an allosteric mechanism of action involving restriction of motion between two mobile RNAP modules. Identification of the binding site allows prediction of bacterial species in which ppGpp exerts its effects by targeting RNAP.

  13. FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase

    OpenAIRE

    Tiraidis, C.; Alexacou, K. M.; Zographos, Spyros E.; Leonidas, Demetres D.; Gimisis, T.; Oikonomakos, Nikos G.

    2007-01-01

    FR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b–FR258900 complex and refined it to 2.2 Å resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where th...

  14. Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin.

    Directory of Open Access Journals (Sweden)

    Alessio Bocedi

    Full Text Available Human serum albumin (HSA, the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s. As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i of carbon monoxide (CO binding to ferrous human serum heme-albumin (HSA-heme-Fe(II by warfarin (WF, and (ii of WF binding to HSA-heme-Fe(II by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II, respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands. This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II. The HSA-heme-Fe(II populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i upon CO binding a conformational change of HSA-heme-Fe(II takes place (likely reflecting the displacement of an endogenous ligand by CO, and (ii CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II.

  15. Characterization of an allosteric citalopram-binding site at the serotonin transporter

    DEFF Research Database (Denmark)

    Chen, Fenghua; Breum Larsen, Mads; Neubauer, Henrik Amtoft;

    2005-01-01

    -citalopram, sertraline,       serotonin and paroxetine. EC50 values for S- and R-citalopram are 3.6 +/-       0.4 microm and 19.4 +/- 2.3 microm, respectively. Fluoxetine, venlafaxine       and duloxetine have no significant effect on the dissociation of       [3H]S-citalopram. Allosteric modulation of dissociation...

  16. Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

    Science.gov (United States)

    Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

    2013-09-01

    Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

  17. Markov propagation of allosteric effects in biomolecular systems: application to GroEL–GroES

    OpenAIRE

    Chennubhotla, Chakra; Bahar, Ivet

    2006-01-01

    We introduce a novel approach for elucidating the potential pathways of allosteric communication in biomolecular systems. The methodology, based on Markov propagation of ‘information' across the structure, permits us to partition the network of interactions into soft clusters distinguished by their coherent stochastics. Probabilistic participation of residues in these clusters defines the communication patterns inherent to the network architecture. Application to bacterial chaperonin complex ...

  18. Coupled Dynamics and Entropic Contribution to the Allosteric Mechanism of Pin1.

    Science.gov (United States)

    Barman, Arghya; Hamelberg, Donald

    2016-08-25

    Allosteric communication in proteins regulates a plethora of downstream processes in subcellular signaling pathways. Describing the effects of cooperative ligand binding on the atomic level is a key to understanding many regulatory processes involving biomolecules. Here, we use microsecond-long molecular dynamics simulations to investigate the allosteric mechanism of Pin1, a potential therapeutic target and a phosphorylated-Ser/Thr dependent peptidyl-prolyl cis-trans isomerase that regulates several subcellular processes and has been implicated in many diseases, including cancer and Alzheimer's. Experimental studies suggest that the catalytic domain and the noncatalytic WW domain are allosterically coupled; however, an atomic level description of the dynamics associated with the interdomain communication is lacking. We show that binding of the substrate to the WW domain is directly coupled to the dynamics of the catalytic domain, causing rearrangement of the residue-residue contact dynamics from the WW domain to the catalytic domain. The binding affinity of the substrate in the catalytic domain is also enhanced upon binding of the substrate to the WW domain. Modulation of the dynamics of the catalytic domain upon binding of the substrate to the WW domain leads to prepayment of the entropic cost of binding the substrate to the catalytic domain. This study shows that Ile 28 at the interfacial region between the catalytic and WW domains is certainly one of the residues responsible for bridging the communication between the two domains. The results complement previous experiments and provide valuable atomistic insights into the role of dynamics and possible entropic contribution to the allosteric mechanism of proteins. PMID:27077947

  19. TOWARD UNDERSTANDING ALLOSTERIC SIGNALING MECHANISMS IN THE ATPASE DOMAIN OF MOLECULAR CHAPERONES

    OpenAIRE

    Liu, Ying; Bahar, Ivet

    2010-01-01

    The ATPase cycle of the heat shock protein 70 (HSP70) is largely dependent on the ability of its nucleotide binding domain (NBD), also called ATPase domain, to undergo structural changes between its open and closed conformations. We present here a combined study of the Hsp70 NBD sequence, structure and dynamic features to identify the residues that play a crucial role in mediating the allosteric signaling properties of the ATPase domain. Specifically, we identify the residues involved in the ...

  20. Modulation in selectivity and allosteric properties of small-molecule ligands for CC-chemokine receptors

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Malmgaard-Clausen, Mikkel; Engel-Andreasen, Jens;

    2012-01-01

    Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 μM). Besides being agonists, they acted as selective allosteric enhancers of CCL3...... exploration of chemokine receptors as possible targets for therapeutic intervention....